3613 results for "*geneti*"

in 60.39 milliseconds.

• Blood Group Genotypes and Phenotypes in Omani Blood Donors and Its Links With Susceptibility to Malaria

  The Omani population experienced endemic malaria prior to eradication in the late 1990's. Since malaria is known to be a strong selective pressure on the human genome, particularly at blood group associated loci, we aimed to understand how selective pressures from malaria may be affecting genetic variation at blood group loci. Blood samples were collected from 100 healthy, Omani blood donors. Serology testing for 10 clinically relevant blood groups and whole genome sequencing (WGS) to an average coverage of 16X were performed on all samples. Additionally, using the WGS data, genetic variants (SNPs and INDELs) were called for chromosomes 1 - 22 using GRCh38. We find signals of selection at the Plasmodium vivax associated locus, ACKR1 (the Duffy blood group), but not at any Plasmodium falciparum associated loci. We also characterized several previously undescribed blood group alleles in the Omani population affecting antigenic expression, mostly at the RHD, RHCE, and GYPB loci. The data available from this project include BAM files from 100 Omani samples aligned to GRCh38, per chromosome VCF files, and results from the serology tests for all 10 blood groups.

  Study phs003694

• Immunogenetics of BCG Vaccination and Pediatric Tuberculosis

  We examined genetic variation associated with BCG-induced innate immune responses and susceptibility to pediatric tuberculosis (TB) disease. South African study participants were enrolled at the South African Tuberculosis Vaccine Initiative (SATVI) as part of a larger BCG vaccination study. This area has one of the highest rates of TB incidence in the world. Infants were vaccinated with BCG at birth, and a nested case-control study was performed over a 2-year prospective observation period, which resulted in 135 infant TB cases and 521 controls. Whole blood was collected from BCG vaccinated infants at 10 weeks of age. Genotyping was performed with the llumina MegaEx Beadchip, and GWAS was performed against TB disease to assess for associations between genetic variants and susceptibility to TB. In addition, a subset of infants were assessed for BCG-induced innate immune responses (N=198). For these, whole blood was stimulated with BCG or media and flow cytometry was used to measure BCG-induced PDL1, CD40, and cytokine expression in myeloid (mDC) and plasmacytoid (pDC) dendritic cells, monocytes, and neutrophils. Cellular GWAS was then performed to associate genetic variants with BCG-induced immune responses.

  Study phs003406

• Heterogeneity in Lysosomal Storage Disorders

  Gaucher disease (GD) is an inherited lysosomal storage disorder caused by biallelic pathogenic variants in GBA1, which encodes glucocerebrosidase. Additionally, GBA1 variants are a well-established genetic risk factor for Parkinson's disease (PD), leading some PD research centers to incorporate GBA1 screening to identify patients who may benefit from targeted therapeutics. However, detecting GBA1 variants remains challenging due to the gene's high sequence homology with its pseudogene, which can give rise to complex recombinant alleles. This study evaluates the performance of Gauchian, a recently developed software tool for identifying GBA1 variants from whole genome sequencing (WGS) data. The assessment was conducted in a cohort of 90 individuals with GD and five GBA1 heterozygotes, all previously characterized through Sanger sequencing. While Gauchian successfully identified the most common genotypes, it demonstrated limitations in detecting rare or de novo variants due to its restricted internal database and heavy reliance on intergenic structural variants. These limitations led to misclassified homozygosity, incomplete genotyping, and undetected recombination events, ultimately reducing the tool's utility for comprehensive variant screening and precluding its application in diagnostic settings. The study dataset includes WGS from the 90 individuals used in the Gauchian pipeline. This data will be available through dbGaP to facilitate further research on GBA1 variant detection, genotype-phenotype correlations in GD and PD, and the development of improved bioinformatics tools for complex variant identification.

  Study phs003459

• Preclinical In Vitro Studies of Prenatal Treatment of Down Syndrome to Improve Brain Development and Neurocognition

  Down syndrome results from trisomy for human chromosome 21 and is the most frequent genetic cause of intellectual disability. There are no effective treatments for Down syndrome that improve brain development and neurocognition. Altered brain development occurs before birth in Down syndrome, which suggests that the optimal time to initiate therapeutic treatment is during prenatal development. In this study, neural progenitor cell (NPC) cultures were derived from induced pluripotent stem cells (iPSCs), to provide an in vitro model system to examine the effects of trisomy 21 (T21) on neurodevelopment and to measure the ability of pharmacological interventions to alleviate these effects. Gene expression was examined using bulk RNA-Seq in untreated T21 and euploid (control) NPCs and in NPCs treated with the candidate therapeutic molecules fasudil, apigenin, epigallocatechin-3-gallate (EGCG), isoxsuprine, and sphingosine. The results showed that the Rho-associated coiled-coil kinase (ROCK) inhibitor fasudil significantly downregulated expression of inflammatory pathway genes in T21 NPCs, of relevance because elevated inflammatory pathways are present in T21 and may contribute to deleterious phenotypes. Data available through dbGaP include five bulk RNA-Seq datasets from euploid and T21 NPC treated with the five molecules listed above, along with untreated euploid and T21 NPCs. Global protein expression data and phosphoproteomic profile data summary files, generated by tandem mass tag (TMT) mass spectrometry, are also available from untreated euploid and T21 iPSCs and NPCs.

  Study phs004455

• Kids First: Hear-'n-Seq Sequencing for Hearing

  One in 100 children will lose significant hearing by school age with hearing loss of 40 decibels or more, making hearing loss one of the single most common structural defects affecting the pediatric population. Hearing loss can affect a child's ability to develop speech, language, cognitive and social skills. The earlier a child with hearing loss starts receiving appropriate medical and educational services, the more likely they are to reach their full potential. More than half of early hearing loss is due to genetic factors. Approximately 1 in 500 babies is born with hearing loss. While the majority of prelingual hearing loss is nonsyndromic, over 400 syndromes have been described that have hearing impairment as a component. It is critically important to identify the etiology of hearing loss for many reasons, as there may be important health surveillance implications particularly with syndromic causes. Genetic testing is available for congenital hearing loss, but the current standard of care is by no means comprehensive because: 1) many types of genetic variants in known hearing loss genes are not detectable by clinical testing, and 2) it is estimated that more than 100 hearing loss genes are as yet unknown. With this proposal, called Hear-'n-SEQ, we will leverage the resources of the NIH Common Fund's Gabriella Miller Kids First Pediatric Research program to "seek-out" the genetic etiology of childhood hearing loss through comprehensive phenotypic and genomic analyses in an international cohort of hearing impaired patients. By sharing both the clinical and sequence data with the pediatric research community we will be empowered to identify genetic pathways that underlie hearing loss as well as pathways shared with other pediatric conditions. This project will be coordinated through the Harvard Medical School Center for Hereditary Deafness (HMSCHD). The Specific Aims of the project are to: (1) build an international consortium to identify and collect well-curated patient clinical information and DNA samples from children with hearing loss and their parents (trios) or carefully selected multiple affected individuals based on the pedigree structure, (2) submit appropriate DNA samples for whole genome sequencing at an NIH-supported sequencing center, and, (3) identify the genetic etiology of hearing impairment in individuals where possible, and integrate the data collectively into a shared data resource. Because of the tremendous genetic heterogeneity inherent in hearing loss, the proposed international collaboration will produce a maximum yield of diverse genetic causes, as it has been well established that different populations segregate distinct concentrations of hearing loss alleles. Therefore we will sample the hearing impaired pediatric populations of parts of Asia (Hong Kong), the Middle East (Turkey), and the US (individuals of European, African American, Central American and Caribbean descent). In addition to identifying novel etiologies for hearing loss, ultimately this work is designed to help create a pipeline for routinely integrating genomic sequencing into clinical diagnostics, generating more refined diagnostic capabilities, and ultimately more targeted therapies or interventions for children with hearing loss.

  Study phs002115

• The Genetic Landscape of Familial Pulmonary Fibrosis

  This dataset was collected from a study that was designed to identify disease-causing rare genetic variants in individuals with Familial Interstitial Pneumonia (FIP). Subjects were identified from our ongoing FIP Registry (IRB #020343), where FIP is defined as idiopathic interstitial lung disease (ILD) in two or more family members with at least one affected individual diagnosed with idiopathic pulmonary fibrosis (IPF). Whole exome sequencing was performed on ~600 affected members from 525 kindreds using genomic DNA isolated from peripheral blood.

  Study phs003750

• Direct Transposition of Native DNA for Sensitive Multimodal Single-Molecule Sequencing

  STUDY GOALS: This study focuses on elucidating the epigenetic modulators of prostate cancer progression and metastasis at high resolution. This is achieved by applying a novel, high-sensitivity single molecule sequencing assay that measures chromatin state on single DNA molecules (SMRT-Tag) to matched primary and metastatic tumor samples from the same patient. Samples are obtained from patient derived xenograft (PDX) models. STUDY DESIGN: Individuals diagnosed with primary and metastatic prostate cancer in the course of routine care were consented and enrolled, and biopsies of primary and/or metastatic lesions performed to obtain sample material used for generating PDX models. Samples collected from these models were processed with a novel strategy developed for highly-sensitive multimodal profiling of single chromatin fibers using the third generation long-read sequencing. The resulting data indicates genetic variants, chromatin organization, and m5dCpG methylation status across the genome. PRINCIPLE FINDINGS: We determined characteristic single-molecule patterns of chromatin organization (spacing of nucleosomes, presence and absence of m5dCpG marks, etc.) that were altered in the transition from primary malignancy to metastasis. Broadly, global chromatin organization was severely disrupted in metastatic samples, resulting in increased accessibility at CTCF motifs, which may be relevant for disease progression. We further identified specific genomic domains including constitutive heterochromatin significantly enriched for irregular or hyper-accessible chromatin. Together, these findings suggest the involvement of ATP-dependent chromatin remodelers in evicting nucleosomes as a facet of metastatic prostate cancer. DATA AVAILABILITY: SAMOSA-Tag, the assay used in this study, is a sequencing assay that uses the third generation long read sequencing, specifically the SMRT sequencing platform from Pacific Biosciences. Demultiplexed raw SMRT sequencing BAM files generated in this study are deposited. Individual raw subread BAM files correspond to replicate sequencing assays performed on either primary or metastatic PDX prostate tumors.

  Study phs003511

• Collaborative Cohort of Cohorts for COVID-19 Research (C4R): Prevent Pulmonary Fibrosis (PrePF)

  Cohort Description Prevent Pulmonary Fibrosis (PrePF) has been investigating the clinical, physiologic and genetic phenotypes of interstitial lung disease (ILD) by focusing on families with two or more cases of ILD and individuals with sporadic IPF. It has recruited over 1,200 families with two or more cases of pulmonary fibrosis. These families with pulmonary fibrosis include 2,837 individuals with probable or definite idiopathic interstitial pneumonia (IIP) and 2,404 unaffected FDRs. In addition, PrePF recruited over 10,000 individuals with sporadic idiopathic pulmonary fibrosis (IPF). Data Being Submitted Wave 1 questionnaire data includes 397 variables for up to 585 PrePF participants in C4R Wave 2 questionnaire data includes 448 variables for up to 370 PrePF participants in C4R Dried Blood Spot/Serosurvey data includes 7 variables for up to 206 PrePF participants in C4R Derived data includes 43 variables for up to 585 PrePF participants in C4R Phenotype data includes 113 variables for up to 585 PrePF participants in C4R

  Study phs002975

• The Effects of Long-Term Heavy Metal Exposure on Transcriptome Landscape in Human Peripheral Blood Cells

  The present study investigates the impact of long-term residence in a mining area on transcriptome changes induced by heavy metal exposure in human peripheral blood mononuclear cells (PBMCs) from 65 healthy subjects selected from the general population. This study includes the same participants which were recruited in our previous investigation on heavy metal long-term environmental exposure-related gene-specific methylation changes (phs003392.v1.p1). We performed a differential expression analysis to compare the mRNA transcriptome of 31 residents from the mining region (MRR) - individuals living in the Kapan mining area with reported environmental exposures to heavy metals - with that of 34 residents from non-mining regions (NMR) - individuals residing at a considerable distance from mining locations. We also evaluated the potential association of gene expression profiles with the blood metallome, including levels of Ca, Mg, Co, Fe, Mn, Cu, Mo, Se, Zn, As, Sb, Tl, Be, V, Ni. Poly-A selected strand-specific mRNA library was prepared with Illumina Stranded mRNA Prep kit. The sequencing was performed on the Illumina NovaSeq-6000 platform with 38.5 million single-end 100 bp reads on average generated per sample. Quality checking of the sequencing data was performed using Illumina Basespace reports and the program FastQC (V0.10.1). Reads were aligned against the Human Genome Hg38 using STAR (version 2.7.1a). According to our findings, long-term residence in a mining area is correlated with alterations in the blood transcriptome, with responses varying by sex. Pathway analysis revealed upregulation of immune response related pathways, and downregulation of translation and ribosome biogenesis in the PBMCs of the MRR. Pathways related to metal ion transmembrane transport, epigenetic modifications (histone deacetylases (HDACs) and DNA methylation) were upregulated in males, while in females mostly transcripts involved in inflammation and cytokine mediated signaling were upregulated. Additionally, among the dysregulated pathways, the TNF-α signaling via NF-κB showed opposite changes in females and males.

  Study phs003657

• Understanding Determinants of Racial Disparities in Lung Cancer Incidence

  This is a nested case-control study designed to evaluate the association between common genetic variants and the risk of lung cancer. The study included 1258 cases and 1252 controls selected from the Southern Community Cohort Study (SCCS), a large, prospective observational cohort. Cases were identified from cancer registries across the catchment area of the SCCS. Cases and controls were frequency matched on age, sex, race, and enrollment site (community health center vs general population).

  Study phs003789

• Assessment of Epigenetic and Transcriptomic Signatures During Induced Neural Stem Cell Conversion of Human Blood Cells

  Cellular reprogramming by direct cell fate conversion has been shown to be associated with epigenetic de-aging. However, the dynamics of this process still remain elusive. Here, we generated induced neural stem cells (iNSCs) from erythroid progenitors of donors ranging from neonatal to 101 years of age by overexpression of the transcription factors SOX2 and MYC. First, performing DNA methylation analyses, we corroborated our previous finding that iNSCs generated from aged donors show pronounced epigenetic de-aging (data deposited as GSE295849). Studying the dynamic of epigenetic de-aging during iNSC conversion across time, we found that this process is largely protracted. Second, RNA sequencing analysis revealed that transcriptomic differences between young and old donor-derived iNSCs dissipate with extended time in conversion, too (data available through dbGaP). Concordant with this observation, established iNSC lines lack age-associated cellular hallmarks, similar to induced pluripotent stem cells and their derivatives. Finally, time course analyses on epigenome and transcriptome level both revealed that acquisition of a bona fide NSC signature extends greatly beyond the time point when proliferative PAX6-positive iNSCs emerge.

  Study phs004047

• Assessing Molecular GxT Interactions in Neural Progenitors Exposed to Valproic Acid and Lithium

  In this study we aimed to identify context-dependent regulatory functions of common genetic variation after stimulation with clinically relevant molecules, valproate and lithium. Fetal cortical tissue between 14 and 21 weeks gestation was subjected to RNA-Sequencing (232 samples) and ATAC-Sequencing (232 samples) to profile expression and chromatin accessibility, respectively. Considering donor genotypes, we were able to identify eQTLs, caQTLs, as well as response QTLs of both categories. The dataset provided here includes 232 RNA-sequencing files in bam format and 232 ATAC-sequencing files in bam format. We also provide 83 donor genotypes in VCF format (hg38). NOTE: Some sequence data files used in this study were previously submitted for phs003642.v1.p1 NIMH/Wnt_NeuralProgenitors. Investigators requesting access to data from phs004321 should also apply for access to phs003642.

  Study phs004321

• Integrating Contemporary Biospecimens and Immunomethylomics into the study of the Glioma Genetics and Immunity - CIDR

  Gliomas account for 80% of all malignant brain tumors and have an extremely poor prognosis, with a 5-year survival of 5.1%. The etiology of glioma remains poorly understood, with few established modifiable risk factors. Multiple studies have implicated infections in the development of glioma; however, the underlying mechanisms and putative causal pathogens remain unclear. In addition to risk, we have recently shown that reactivity to varicella zoster virus is also associated with a significant survival benefit in patients with glioma. Previous epidemiologic studies have investigated a limited number of pathogens using serological assays that only allowed detection. Recent analyses from our group have also highlighted that glioma subtypes have varying immune cells at diagnosis, and that there may be prognostic value. This CIDR proposal has two parts to add to the parent R01- Discovering Infection-mediated Pathways of Glioma Etiology and Prognosis by Leveraging Multiplex Serology and Immunogenomics (R01 CA266676) that applies multiplex serology and targeted HLA sequencing to understand the interplay between germline genetics, antigen reactivity and glioma risk/survival. In the first part of this application, we seek to expand our current plans to include 447 Immune Profiles Study subjects that have contemporary treatment, and highly detailed longitudinal biospecimens and clinical data measured at every clinic visit across the course of treatment. We plan to genotype these subjects for inclusion in viral antigen measurement and HLA sequencing. We will also include 30 cross-study replicate samples from the UCSF Adult Glioma Study (dbGaP Study Accession: phs001497) in this genotyping project. The second part of this CIDR proposal seeks to analyze whole blood methylation to deconvolute blood cell proportions for 1592 glioma cases and 1147 matched controls from the Adult Glioma Study that do not have existing blood methylation. The derived blood cell proportions will facilitate a deeper understand of the subtype specific risk and prognosis associated with immune cell traits, integrate mediation by germline genetics, and hone the antigen associations by controlling for antigen presenting cells. This proposal will unite two parallel, but independent and complementary studies, and will complete the viral, immunologic and genetic understanding of the association with viral reactivity and immune cells that will pave the way for functional studies. This will allow us to develop comprehensive immunogenomic models for predicting glioma risk and survival. Taken together, the proposed study will contribute new, high-quality data that will significantly advance our understanding of glioma pathogenesis, as well as inform avenues for prevention and improvement of outcomes in glioma patients.

  Study phs003990

• Clonal Heterogeneity in Human Pancreatic Ductal Adenocarcinoma and Its Impact on Tumor Progression

  This study of primary human pancreatic ductal adenocarcinoma (PDAC) tumors (n=62) aims to characterize intratumoral clonal diversity, transcriptional plasticity, tumor–microenvironment interactions, and spatial patterns associated with progression and metastasis. Combined single-cell RNA sequencing and spatial transcriptomics enabled reconstruction of tumor phylogenies and mapping of clone-specific transcriptional states. Extensive intratumoral heterogeneity was observed, with multiple genetically distinct neoplastic clones coexisting within tumors. Distinct clones exhibited unique interactions with stromal and immune cells, and dispersed clones enriched for epithelial-to-mesenchymal transition (EMT) programs and immune-suppressive microenvironments correlated with metastatic potential and lymph node colonization. A recurrent classical-to-basal clonal transition associated with MYC amplification and reduced immune response was identified and experimentally validated, implicating clonal evolution in emergence of more aggressive phenotypes. Controlled-access dbGaP deposits will include raw sequencing data from single-cell RNA sequencing and spatial transcriptomics experiments and de-identified clinical/sample metadata.

  Study phs004079

• The Genetics of Obesity, Diabetes, and Heart Disease in African Diaspora Populations

  African Americans have one of the highest rates of type 2 diabetes in the United States, and often have other medical problems related to obesity and cardiovascular disease. These conditions have various risk factors, including high blood sugar levels, high cholesterol levels, and insulin resistance. However, these risk factors need further study in individuals with African ancestry, including Afro-Caribbean and sub-Saharan Africa migrant populations. Genetic study of obesity, adult-onset diabetes, heart disease, and other common health conditions in African ancestry individuals across the Diaspora could be particularly informative. Therefore, this study is designed to collect genetic and non-genetic information from individuals with African ancestry to study common health conditions related to obesity, adult-onset diabetes, and heart disease. This ongoing study includes individuals at least 18 years of age who self-identify as African American, Afro-Caribbean, or migrants from sub Saharan Africa. Participants undergo physical examination and provide a blood sample for study. Participants also answer questions about personal and family medical history and current lifestyle behaviors. No treatment is provided as part of this protocol.

  Study phs004382

• Multi-omic Characterization of Genetic Variants in IBD Risk Loci

  This study aims to identify potential target genes of GWAS loci for inflammatory bowel diseases (IBD) by mapping expression quantitative trait loci (eQTL) using colon tissue from a cohort of 252 IBD patients. Results were compared to non-IBD colon eQTL from GTEx and BarcUVa-seq (GTEx Consortium, Science 2020 / Díez-Obrero V et al., Cell Mol Gastroenterol Hepatol. 2021). Statistical colocalization of eQTL and GWAS loci revealed novel colocalizations and target genes using diseased tissue. These eQTL also had regulatory and functional characteristics which were distinct from non-IBD eQTL. Available data includes typed and imputed genotypes, raw total RNA-seq, and association results.

  Study phs003881

• The National Myelodysplastic Syndromes (MDS) Study- Digital Histopathological Slide Images

  The goal of the National MDS Study was to establish a publicly available resource to facilitate the study of MDS natural history. This was accomplished through: 1) Creation of a multi-institutional, rich clinical database with genetic sequencing, longitudinal biorepository of consistently processed and clinically well-annotated blood and tissue specimens collected prospectively from participants with MDS and participants with idiopathic cytopenia of undetermined significance (ICUS); and 2) Support for investigator-initiated studies of MDS that will have high-impact for MDS patients, including basic science, clinical, health outcomes and epidemiological research. The study has assembled a comprehensive worldclass clinical database from over 2,100 participants with suspected or newly diagnosed MDS or MDS/MPN overlap disorders including extensive quality of life assessments, laboratory data, exposure history, histopathology slides and images, targeted and whole genome sequencing data, and hematopoietic and germline tissues representing high-quality biospecimens and data from diverse centers across the United States. These resources are now made available to the scientific community to support investigator-initiated research. The Digital Histopathological Slide Image data set further enhances the characterization of the MDS study cohort. The image library contains a total of 3,988 digital histopathology slides (H&E and Wright stained) of bone marrow aspirate and biopsy samples as well as peripheral blood smears collected from 1,652 MDS participants at baseline and follow-up visits. Clinical data associated with these images includes basic demographics, the central pathologist's WHO classification, and other slide review comments. Additional characterization of the MDS participants is available for further evaluation. The slide image library provides an extensive and unique resource to the research community offering a platform to evaluate new techniques that could potentially lead to improvements in diagnostic screening procedures and classification of patients with MDS.

  Study phs004357

• Collagen XVII Promotes Pancreatic Cancer Through Regulation of PIK3R5

  Pancreatic ductal adenocarcinoma (PDAC) contains a desmoplastic stroma that promotes the aggressive biology of this disease. While the varied mechanisms by which fibrillar collagens contribute to PDAC have been defined, little is known about the contribution of transmembrane collagens. Among this class of collagens, Collagen XVII uniquely contains an extensive intracellular domain that connects intracellular cytoplasmic components with the extracellular matrix. Collagen XVII is best characterized as the defining component of the type I hemidesmosome, an anchoring complex that attaches epithelial cells to the underlying basement membrane. In this study, we characterize the expression of collagen XVII in PDAC and the mechanisms by which it contributes to PDAC biology. We demonstrate that crosstalk between PDAC cells and cancer associated fibroblasts drive collagen XVII expression in vitro and xenograft tumor models in vivo. Genetic depletion of collagen XVII in low-passage patient derived cell lines diminishes their metastatic potential and ability to form tumors in mice. Whole transcriptome sequencing of tumors formed by cells with diminished collagen XVII levels revealed dramatically lower levels of PIK3R5, a regulatory subunit of class IB phosphatidylinositol-3-kinase (PI3K) that interacts with G protein-coupled receptors. Consistent with this, collagen XVII-deficient tumors exhibited lower levels of phosphorylated AKT, a downstream effector of PI3K. The studies highlight the importance of collagen XVII signaling in PDAC and define a novel mechanism by which collagen XVII mediates activation of PI3K.

  Study phs003641

• Retinal Contributions to Vision Loss in Albinism

  The human fovea supports some of our most important visual functions, such as color discrimination and high acuity vision, but there remain significant gaps in our understanding of foveal development and the exact causal relationships between structural pathology and specific visual deficits. This study employs human albinism (a hereditary condition in which the fovea is grossly underdeveloped) as a natural model to examine these and other key issues. Using advanced non-invasive imaging approaches together with genetic testing, we seek to reveal the physiological and anatomical basis for visual deficits in albinism on a personalized basis and to refine the anatomical outcome measures for use in correlative studies and emerging therapeutic trials in albinism. Specifically, given the central role of the fovea in our visual function, this study seeks to elucidate the genetic factors affecting normal foveal development, to advance our understanding of a wide range of conditions associated with altered foveal morphology. Around 300 people will be recruited for this study, with an anticipated ~250 consenting to sharing their data in dbGaP. Next generation sequencing of participant samples will be done to analyze over 100 genes (list below) with links to albinism. Information collected for each sample for inclusion in this study will include: Sequencing-derived raw genetic data of study participants,Demographic data, including age, sex, race, Hispanic ethnicity, and gender identity (in some cases)Albinism phenotypeOther related phenotypic data if/when collected: premature birth, AOSLO retinal imaging, ancillary retinal imaging, visual field & fixation evaluation, color vision testing, and macular pigment optical densityClinical data when possible/available, such as: stereoacuity, BCVA, foveal pit morphology, NIR autofluorescence signal

  Study phs003573

• A Case Controlled Etiologic Study of Sarcoidosis (ACCESS-BioLINCC)

  Data Access NOTE: Please refer to the "Authorized Access" section below for information about how access to the data from this accession differs from many other dbGaP accessions. Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from (ACCESS) include Bronchial Lavage, DNA, Peripheral Blood Mononuclear Cells, and Plasma. Please note that use of biospecimens in genetic research is subject to a tiered consent. Objectives: To determine the etiology of sarcoidosis by establishing a case control, multi-center study. In addition to etiology, this study also sought to examine socioeconomic variables and the clinical course of patients with sarcoidosis, including quality of life.Background: Sarcoidosis is a chronic granulomatous disorder of unknown cause that is characterized by activation of T-lymphocytes and macrophages. For many years, sarcoidosis was presumed to be an atypical manifestation of tuberculosis because of the similarity between the inflammatory responses of the two diseases. However, as culture techniques became more widely employed to diagnose tuberculosis and it became less common, it became clear that sarcoidosis was not simply a variation of tuberculosis. Data on the etiology of sarcoidosis have come from diverse sources: in clinical investigations, alveolitis has been found to precede granulomatous inflammation; in case control studies, familial aggregation has been identified; and in case reports, recurrence of granulomatous inflammation has been observed after lung transplantation. The cause may not prove to be a single, known exposure. Interactions of exposures with genetic dispositions could have important implications for our understanding of immune responses as well as the pathogenesis of sarcoidosis.Participants: 736 participants with sarcoidosis enrolled within 6 months of diagnosis from 10 clinical centers in the U.S. Using the ACCESS sarcoidosis assessment system, organ involvement was determined for the whole group and for subgroups differentiated by sex, race, and age (Conclusions: The initial presentation of sarcoidosis is related to sex, race and age, and it tends to remain stable over two years in the majority of patients. The etiology is probably multifactoral with both genetic and environmental factors contributing.Specimen Details: The PBMC for this study are pelleted and suspended in guanidinium-based solution and are nonviable.

  Study phs004276

• The National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics Resource Center: DNA and Cell Line Repository (the NINDS Repository): Motor Neuron/Amyotrophic Lateral Sclerosis (ALS) Study

  The National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics Resource Center: DNA and Cell Line Repository (the NINDS Repository), banks phenotypic data and biological samples, including from individuals with motor neuron disease, in order to facilitate gene discovery in neurological disorders. Those samples are used in a number of studies, and genotyping data from studies using this resource are encouraged to be shared via dbGaP. Many studies have already shared data in this fashion, which in turn, can be linked back to the biologicals banked at the NINDS Repository. Motor Neuron Disease is characterized by selective degeneration of the motor neurons of the spinal cord, brainstem, or motor cortex. Clinical subtypes are distinguished by the major site of degeneration. In Amyotrophic Lateral Sclerosis (ALS), there is involvement of upper, lower, and brainstem motor neurons. In progressive muscular atrophy and related syndromes, the motor neurons in the spinal cord are primarily affected. With progressive bulbar palsy, the initial degeneration occurs in the brainstem. In primary lateral sclerosis, the cortical neurons are affected in isolation (Adams et al, Principles of Neurology, 6th ed, p 1089). The Motor Neuron Disease Collection of DNA and cell lines in the NINDS Repository is largely Amyotrophic Lateral Sclerosis cases (others include progressive muscular atrophy, primary lateral sclerosis, progressive bulbar palsy, Kennedy's disease). Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). Although ALS is the most common MND, it is still a relatively rare disease with an incidence of around 1.6 per 100,000 in the United States. It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered (including SOD1). However, most forms of the disease are not obviously familial. It is suspected that the sporadic forms of neurodegenerative disorders are caused by multiple genetic variants that individually make relatively weak contributions to risk. There is also an associated Control collection (see dbGaP and Coriell). Studies in motor Neuron Disease may use cases from the NINDS repository, controls from the NINDS repository, as well as cases, and controls, from other sources. A subset of subjects from The National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics Resource Center: DNA and Cell Line Repository (the NINDS Repository): Motor Neuron/Amyotrophic Lateral Sclerosis (ALS) Study was utilized in the Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data study. Note: The publication Chio et al., 2009 states that "Raw sample-level genotype data from the initial GWAS study ... are available for download through the dbGAP portal (phs000006.v1.p1)". Instead, please follow this link: phs000101.v1.p1.

  Study phs000006

• Substance Use and Immunity in HIV+ Adolescents by Systems Biology

  Marijuana contains a complex variety of unique cannabinoids, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), known to impact inflammatory and lymphocyte activation pathways in the lymphoid tissues and brain. While marijuana continues to be classified under United States federal law as an illegal drug, medical use of cannabis is legal in at least 35 states, including 16 states and the District of Columbia where recreational marijuana is approved for individuals over the age of 21. In many states HIV infection is the sole indication for the use of medicinal marijuana as adjuvant therapy. Cannabis is effective in the treatment of HIV-associated peripheral neuropathy, improves appetite, and enhances overall quality of life of people with HIV while the anti-inflammatory effects of cannabis may improve HIV-associated complications. However, few studies have examined the effect of recreational or medicinal cannabis use on inflammatory pathways in peripheral blood cells among individuals with HIV. The goal for this study is to assess the anti-inflammatory effect of recreational marijuana use by YWH. Using a systems biology approach, unique genetic and cellular pathways within the peripheral blood cell transcriptome in a population of virally suppressed YWH on ART who used marijuana, alone or in combination with tobacco, compared to a reference group of youth without HIV.

  Study phs002090

• The Electronic Medical Records and GEnomics Network Genomic Risk Assessment (eMERGE IV)

  The eMERGE (electronic MEdical Records and GEnomics) network enrolled ~25,000 individuals not typically involved in research in a prospective cohort study across 10 sites. The network developed methods to return cross-ancestry polygenic risk scores, monogenic risks, family history, and clinical risk assessments via a genome-informed risk assessment (GIRA) report along with recommended actions. The GIRAs include summary care recommendations for 11 conditions, education pages, and clinical laboratory reports and was returned to participants, their providers, and their EHR. The network is examining the uptake of care recommendations after return of results.Children's Hospital of Philadelphia (CHOP)The Center for Applied Genomics (CAG) is a specialized Center of Emphasis at the Children's Hospital of Philadelphia (CHOP) with the primary goal of translating basic research findings to medical innovations. The mission of CAG is to develop new and better ways to diagnose and treat children affected by rare and complex medical disorders. We aim to discover genetic causes for the most prevalent diseases of childhood including ADHD, asthma, autism, diabetes, epilepsy, obesity, schizophrenia, pediatric cancer, and a range of rare diseases. Ultimately, our objective is to generate new diagnostic tests and to guide physicians to the most appropriate therapies. Our participants are recruited from the CHOP Health Care Network, which includes over 50 sites throughout Pennsylvania and New Jersey, 100% of which use Epic EMR system. This constitutes the country's largest pediatric integrated delivery system, supporting >1.1 million visits/year within the primary and specialty care networks, community-based inpatient pediatric and neonatal programs, a rehabilitation hospital, and a home care service. It provides acute- and well-care to patients in urban, rural, and suburban settings.Cincinnati Children's Hospital Medical Center (CCHMC)CCHMC has proposed ambitious initiatives for eMERGE IV. The major goals are to generate, return as appropriate along with clinical recommendations, individualized genomic risk assessments that include polygenic risk scores for 2500 minority participants ascertained on dyads (mother/child) and extended to families (dyad + biologic father, siblings). The informatics initiatives include integration of electronic medical records and development, implementation and evaluation of clinical decision support at two different hospital systems, one pediatric and one adult. Participant preferences, education needs, and ethical and social implications will be studied throughout the 5 year period. Columbia UniversityColumbia University in partnership with the New York-Presbyterian hospital has a long and strong tradition of patient-centered research and community engagement in the urban, medically underserved communities of Washington Heights and Harlem in Northern Manhattan, and has established Precision Medicine as a major university-wide initiative (PMI), of which eMERGE is a vital program. We possess broad and deep expertise in clinical genetics, genomics, informatics, EHR phenotyping, systems biology, public health, and ELSI, including return of genetic results and secondary findings to diverse patients. Columbia will share lessons learned in linking EHR and sequence data for genomic decision support, developing scalable genomic education methods and assessing the impact of returning genetic results on patients, families, and clinicians. We are poised to contribute novel comprehensive risk prediction and management solutions for diverse patients as part of eMERGE IV efforts.Icahn School of Medicine at Mt. Sinai (Mt. Sinai)Mt. Sinai investigators have been at the center of many NHGRI-led genomic research (GSP, PAGE) and genomic medicine (eMERGE, CSER, IGNITE) consortia. Building on our decade-long track record in genomic research, clinical trials, and genomic medicine in diverse, underserved patients from New York City, we propose to develop new frameworks to bring genomic risk into clinical care to promote health equity. In addition to genomic discovery and risk prediction, we are creating analytical and data resources, and digital health applications tailored to diverse populations, as part of the eMERGE IV Network. The Mt. Sinai team is composed of clinicians and scientists who work closely with community members and industry partners to develop flexible and innovative strategies to bring leading-edge research into clinical care. Having recently announced a large institutional investment to scale the integration of genomics and artificial intelligence into patient care, Mt. Sinai is poised to contribute to eMERGE IV's mission to implement and learn from genomic risk assessment in clinical care. Mt. Sinai's team will contribute to progress in multiple areas across eMERGE, including developing and deploying electronic phenotypes; discovering new genotype-phenotype associations; and facilitating the communication of genomic results to patients and their healthcare providers.Mass General BrighamThe eMERGE IV Clinical Center at Mass General Brigham leverages a large biobank, clinical data in the electronic health records (EHR) for >6 million patients from the largest integrated health care provider in New England, advanced bioinformatics expertise, prior leadership in PRS development, established expertise in returning genomics results, and experience using information technology to transform clinical processes and assess medical, behavioral and economic outcomes. We have developed highly specific machine learning algorithms for e-phenotypes and implemented eMERGE algorithms for multiple phenotypes and have considerable experience in developing decision support tools and analyzing outcomes that can be leveraged to study the integration of PRS data into clinical practice. We will test the hypothesis that PRS will allow us to stratify eMERGE participants based on genetic risk for common complex traits. We will focus on coronary artery disease, atrial fibrillation, type 2 diabetes, colorectal cancer and depression in GWAS populations and validate multi-ethnic PRS in the Mass General Brigham Biobank and eMERGE III dataset. We will conduct an analysis of the effect of disclosing results to high risk participants to determine how personalized results changed patient outcomes in laboratory values, risk reduction behaviors, or health care utilization.Mayo Clinic (Mayo)The goal of Mayo eMERGE investigators is to leverage the electronic health record (EHR) for genomic discovery and to implement genomic medicine to improve health care outcomes, working closely with other eMERGE sites and the Mayo Center for Individualized Medicine. In eMERGE I we used genotype data and electronic phenotyping algorithms for genomic discovery. In eMERGE II we conducted a clinical trial of disclosing a polygenic risk score (PRS) for coronary heart disease (CHD) and placed pharmacogenomic variants in the EHR with linkage to clinical decision support (CDS). In eMERGE III, we returned actionable findings from targeted sequencing of 68 genes and collaborated with a Federally Qualified Health Center (FQHC) to bring genomic medicine to an under-represented population. In eMERGE IV, as part of the Genomic Risk Assessment & Management Network, we will test the hypothesis that individuals at high polygenic risk for common diseases will have a higher uptake of risk reduction measures than those at lower risk. We will build on our prior work in genomic discovery, EHR integration and return of results (RoR) to develop and validate PRS and combine these with clinical risk scores and family history to compute comprehensive risk profiles for 2500 individuals. Our prior work in disclosing a PRS for CHD to research participants as part of a comprehensive risk profile enables us to efficiently expand the approach to other common diseases that pose a significant public health burden. To assess the utility of PRSs, we will recruit 1800 adults and 200 adolescents from Rochester MN and 500 adults from Phoenix AZ. DNA will be sent for CLIA-certified genomic testing and we will calculate ancestry specific PRSs for each participant. Individualized risk estimates will be reported to participants and health care providers (HCPs) and placed in the EHR with linkage to CDS that includes guideline-based risk-management information. For participants who are at significantly higher polygenic risk of developing at least 1 of the diseases, results will be disclosed in-person by a HCP followed by assessment of outcomes including new tests ordered, risk reduction measures, and changes in modifiable risk factors. We will examine the economic, behavioral and psychosocial implications of returning PRS. Our focus on PRS for common cardiovascular diseases brings genomic medicine to the population. We will continue our partnership with Mountain Park Health Center, a FQHC serving low-income, minority communities in Phoenix AZ, to address concerns about health disparities in the context of genomic medicine.Northwestern University (NU)Northwestern University is dedicated to translational genomics, with a strong focus on unified, interdisciplinary research bridging the informatics, clinical, basic science, and bioethics domains. Over the phases of eMERGE, Northwestern has applied this interdisciplinary approach to study the feasibility, utility, outcomes, and effectiveness of EHR-linked genomic information as a member of the network. Particular areas of focus include: novel informatics approaches to integrate genomic results into EHR systems; development of open-source, EHR-based phenotyping algorithms to empower translational research across a variety of clinical domains; and studies of participant, patient, and provider interaction with EHR-based genomic results. In phase IV of eMERGE, Northwestern is building on this expertise to develop, deploy, and evaluate systems of EHR-based, genomics-guided clinical risk assessment and management tools across a variety of common, impactful conditions. Northwestern's cross-disciplinary approach to this work is empowered by an innovative smartphone app to consolidate outreach, enrollment, engagement, return of results, and dissemination of health education materials surrounding genetic risk and risk management. Focusing recruitment on community-based clinics, Northwestern aims to engage participants from communities that, though not traditionally included in academic research settings, could benefit significantly from these risk management approaches. By combining expertise in informatics and EHR integration with innovative return-of-results strategies rooted in behavior theory, Northwestern aims to provide valuable data on accuracy, utility, and uptake of genetic risk assessment as the field moves towards integrating genetic risk scores into clinical practice.University of Alabama at Birmingham (UAB)Our eMERGE team aims to bring our experience and expertise in research with medically underserved (>75%) populations to identify genomic signatures of common diseases, conduct genomic risk assessments within the clinical workflow and where appropriate, pre-treat at-risk patients with common diseases including diabetes, chronic obstructive pulmonary disease, obesity, coronary artery disease and prostate cancer. Our aims will also allow us to develop genomic risk assessments, and address challenges involved in bringing genomic medicine into routine medical care. Working with the eMERGE network, we will select the eleven diseases of public health impact and select polygenic risk scores for clinical implementation. We will conduct an ethical legal social implications (ELSI) study, to explore patient perspectives on the use of family history and polygenic risk scores for estimating disease risk among Alabama Genomic Health Initiative (a statewide cohort) participants. The results will inform the development of consent, educational materials, and a communication strategy to enhance recruitment and retention of eMERGE participants. Recruiting over 75% of patients from medically underserved communities, we will incorporate genomic risk, family history, and clinical data to identify high-risk patients, recommending risk reduction recommendations in concordance with practice guidelines. For high-risk patients, we will deploy clinical decision support and present the genomic risk assessments and risk reduction recommendations. We will assess three outcomes: uptake of recommendations (implementation outcome), adherence to clinic visits (engagement outcome), and surrogates of disease/control (clinical outcome; e.g. blood sugar, cholesterol). We bring our expertise and experience to collaborate with the eMERGE investigative team to leverage the power of genomics to prevent disease.University of Washington (UW)The eMERGE IV Northwest partnership includes clinicians, scientists, and professionals in other fields from University of Washington (UW) Medicine, UW Health Sciences, the Fred Hutchinson Cancer Research Center, and the Brotman Baty Institute for Precision Medicine. The eMERGE IV Northwest partnership aims to evaluate the use of genomic information in the health care of diverse participants at the University of UW. Our site is expected to lead work on the prediction of colon cancer, glaucoma, and cardiovascular disease; other conditions expected to be studied include diabetes, liver disease, high cholesterol, and osteoporosis. Working with our eMERGE colleagues, we will aggregate, into a single score that informs about the risk of a disease, a participant's polygenic test information, which looks at variants from across the genome, as well as other known risk factors, such as personal and family medical history, environmental and social determinants, and physical and lab results. This score would let clinicians know which patients might benefit from screenings or other interventions to reduce the risk of disease or make an early diagnosis. In addition to experts specializing in each of the medical conditions that are the focus of the Northwest site, leaders in health economics, and in the ethical and societal aspects of genomics and health care will also be part of the research team. Medical, as well as economic, outcomes will be measured. Stakeholder engagement will be encouraged to obtain comments from participants and their families.Vanderbilt University Medical Center (VUMC)Vanderbilt University Medical Center has embraced Personalized Health and Healthcare as a key pillar of our Research Strategic Plan. This institutional commitment has taken multiple forms including the development of key infrastructure resources (the institutional Biobank (BioVU); the program in preemptive pharmacogenetic testing; the genotyping and sequencing core) and support of faculty in key disciplines such as genomics, informatics, ethics, privacy science, and clinical pharmacology. VUMC's team has contributed importantly to progress in multiple areas across eMERGE, including developing and deploying phenotype algorithms; developing and managing the genotype quality control pipeline for the network (eMERGE I); discovering new genotype-phenotype relations in VUMC and cross-network datasets; actively participating in the PGx clinical implementation project, community consultation, and return of results initiatives; developing methods to resolve tensions between data access and individual privacy; developing sampling methodology for the CERC survey; and developing new software tools for the field, including for developing and validating phenotypes, de-identification and for the phenome-wide association study paradigm (“PheWAS”)eMERGE Network Coordinating Center (CC)Vanderbilt University Medical Center has been the coordinating center of the eMERGE Network since inception. During this phase of eMERGE we have partnered with the Broad Institute to to add expertise in large-scale genotyping, cloud computing, and genomic data analysis and management, and with Duke University to leverage its proficiency in the implementation of patient-oriented family history tools and delivery of risk assessments. To meet the needs of the Network, the CC continues to serve NHGRI, the Network, and its members in all coordination, communication, and collaboration functions while providing a nationally visible home for eMERGE authored tools and scientific productivity. The CC is also assisting the Network with selecting and validating polygenic risk scores (PRS) for approximately eleven complex diseases and developing genomic risk assessments (GRAs) which combine the PRS with other clinical risks, family history, and monogenic risks. Finally, The CC will coordinate a prospective study for 25,000 participants which calculates clinical and genomic risks for participants and their providers. In addition to providing the genotyping and PRS reporting services, we will develop with the Network scalable EHR-based methods to assess uptake of risk-reduction recommendations and clinical impact.

  Study phs003905

• RNA Transcriptomic and DNA Methylation Landscape in FTLD-TDP and Controls

  Frontotemporal lobar degeneration (FTLD) is one of the leading causes of dementia in individuals younger than 65 years, with the aggregation of TDP-43 as one of the most common forms of FTLD. FTLD-TDP is clinically, genetically and pathologically heterogeneous, with GRN and C9orf72 as the most common genetic forms (although more than 50% of the cases are genetically unexplained), and A, B and C as the most common pathological subtypes. To investigate the molecular differences between the different forms of FTLD-TDP, we performed bulk RNA sequencing (RNAseq) and reduced representation bisulfite sequencing (RRBS) from different brain regions of FTLD-TDP patients and controls. The RNAseq dataset includes samples from the frontal cortex of 149 individuals, comprising 127 FTLD-TDP cases (genetically unexplained types A (27), B (20) and C (22), 24 GRN mutation carriers, and 34 C9orf72 expansion carriers) and 22 controls. The RRBS dataset includes samples from the frontal cortex of 158 individuals —119 FTLD-TDP cases (genetically unexplained types A (25), B (24), and C (25), 20 GRN mutation carriers, and 25 C9orf72 expansion carriers) and 39 controls; and from the cerebellum of 151 individuals —113 FTLD-TDP cases (genetically unexplained types A (24), B (21), and C (23), 20 GRN mutation carriers, and 25 C9orf72 expansion carriers) and 38 controls. In total, the study consists of data from 183 unique individuals, with some overlap across the different datasets.

  Study phs004075

• Genetic Testing to Understand and Address Renal Disease Disparities across the United States (GUARDD-US)

  GUARDD-US is a prospective, multicenter, unblinded, two arm randomized pragmatic clinical trial. Participants will be randomized in a 1:1 ratio to immediate APOL1 gene testing and return of results (ROR) to participant and provider (Intervention arm) versus delayed APOL1 gene testing and ROR to participant and provider (Control arm). The main study will compare outcomes between APOL1 positive participants in the Intervention arm (i.e., early knowledge of APOL1 status) to APOL1 positive participants in the Control arm (i.e., delayed knowledge of APOL1 status). Participants that are APOL1 negative in the Intervention and Control groups will not be included in the main study analyses.Approximately 6,750 participants of African ancestry, age 18-70, with hypertension that either: 1) do not have diabetes and do not have CKD, or 2) have CKD (with or without diabetes) were randomized for the GUARDD-US study. GUARDD-US also includes a substudy to determine the effect of knowledge of genetic test results that predict efficacy of various antihypertensive medications on change in SBP from baseline to 3 months in APOL1 negative individuals at participating sites. The population for the PGx substudy were participants from main study (above) who were randomized to Intervention and who test negative for APOL1. Only participants from PGx substudy participating sites were included in this population.

  Study phs004045

• Virginia PrIMeD Study

  The goal of this study was to determine whether screening children (2-16 yrs) in pediatric waiting rooms for genetic risk of type 1 diabetes (T1D) could be applied to diverse (by geography, genetic ancestry) communities, and for those at "high genetic risk," if barriers prevent subsequent screening for presence of islet autoantibodies. A total of 3,818 children were recruited from eight general pediatric and specialty clinics across Virginia. Clinical Research Coordinators were stationed at each clinic and obtained informed consent/assent, a brief medical history, and a saliva sample for DNA extraction and determination of their genetic risk using a T1D Genetic Risk Score (T1D GRS). Children were present in the clinic for a "healthy" visit, although children with and without a history of T1D were recruited into the study. Age, sex, self-reported ancestry/race, T1D history, and other medical history information was obtained. DNA was extracted from the saliva samples and genotyping with a T1D-focused array using 74 SNPs (including 26 SNPs in the HLA region) provided data to generate a T1D GRS for each individual. Of the 3,818 children recruited, there was a slight excess of males (1,959, 51.3%), a majority of white and Hispanic/Latino ancestry (82.8%), and 91 (2.4%) with prevalent T1D. A total of 542 (14.2%) had "high T1D genetic risk" (T1D GRS > 5). Although the T1D GRS included non-HLA genetic variants, 80% of those with "high genetic risk" would have been classified using only those SNPs in the HLA region alone. Of children with "high genetic risk" and without pre-existing T1D (n=494), 7.0% (34/494) consented for islet autoantibody screening. Among children with pre-existing T1D (n=91), 52% (n=48) also had a "high genetic risk." The HLA-focused T1D GRS was not significantly associated with age at onset of T1D. Of those at high genetic risk that consented for autoantibody testing (n=34) and completed the blood collection (n=28), two (2/28, 7.1%) tested positive for multiple autoantibodies and were at significant risk of developing T1D. Follow up of 55% of parents/guardians identified 2 (of 2,096, 0.095%) participants who developed T1D, one at "high genetic risk" and one with a first-degree relative with T1D. A major factor in obtaining islet autoantibody testing was concern over SARS-Cov-2 exposure and an independent non-scheduled blood collection.Individual-level data at each SNP (genotyped and imputed) for T1D genetic risk and affiliated data are provided in dbGaP.

  Study phs003609

• Prevention and Early Treatment of Acute Lung Injury (PETAL) Network - Functional, Imaging, and Respiratory Evaluation in CORAL (PETAL FIRE CORAL-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.Biospecimens: Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from PETAL FIRE CORAL include plasma and whole blood. Please note that use of biospecimens in genetic research is subject to a tiered consent and biospecimens may not be used to produce commercial products.Objectives: To examine the recovery from COVID-19 disease following acute hospitalization with an emphasis on functional, imaging, and respiratory evaluation, and assess the feasibility of conducting a larger study to evaluate variables associated with differential recovery.Background: The BLUE CORAL study, dbGaP phs003419, was intended to address the knowledge gaps and provide critical data to help guide clinical care, public health, and scientific efforts regarding SARS-CoV-2 (COVID-19) recovery. The understanding and treatment of long-term sequelae of COVID-19, referred to variously as post-acute sequelae of COVID-19 (PASC), post-acute COVID, long COVID, or long-haul COVID, is fundamental to patient recovery. These long-term consequences are common and increasingly recognized, although heterogeneous in manifestation, and can result in a failure to return to baseline level of health. At the time of the FIRE CORAL study, there were limited studies that collected objective assessments following hospital discharge for a wide spectrum of patients surviving COVID-19.Participants: FIRE CORAL enrolled adult participants as a subset of those enrolled in the BLUE CORAL study with a recent COVID-19 hospitalization and that completed the 1- or 3-month post-hospital telephone long-term outcomes assessment. The target enrollment for this pilot study cohort was 80 participants.Design: FIRE CORAL was a multicenter prospective cohort study of participants recovering from COVID-19 disease with in-person follow-up, as an extension of the BLUE CORAL study. The study consisted of a battery of assessments objectively measuring pulmonary function, abnormalities on lung imaging, and functional status. Participants were to attend and perform initial in-person testing at 3 to 9 months after hospital discharge. Participants with abnormal findings on pulmonary function testing or chest imaging during their initial assessment or those with persistent respiratory symptoms were eligible to repeat study procedures 3 months later with a subsequent visit at 12 months. All participants were invited to return for in-person follow up at 12 months after hospital discharge. Assessments included high-resolution chest CT scan without contrast, spirometry, lung volume assessment, diffusing capacity measured by single breath measurement, Six Minute Walk Test, Short Physical Performance Battery, St. George's Respiratory Questionnaire, and Functional Assessment of Chronic Illness Therapy-Fatigue scale. Demographic and hospitalization data are available as part of the BLUE CORAL study.The primary aim of the FIRE CORAL study was to examine the feasibility of conducting rigorous in-person follow-up testing of participants discharged from the hospital following COVID-19 illness to assist with planning for a larger study to evaluate variables associated with differential recovery. The secondary aim was to describe the pulmonary, imaging, and functional recovery following COVID-19 hospitalization in a diverse population of patients.

  Study phs004130

• HudsonAlpha Long Read Sequencing Data of Individuals with Rare Suspected Genetic Conditions

  The data included in this project were generated from several IRB projects focused on the identification of the underlying genetic cause of undiagnosed rare conditions in infants, children and adults enrolled across the southeastern United States. Long read genome sequencing was performed on DNA samples collected as part of an IRB-approved study and findings from this testing was returned to enrolled study participants and the clinical team providing care. Proband participants in these studies were enrolled in both inpatient (neonatal intensive care units) and outpatient settings. When possible, biological relatives (including both biological parents) were also enrolled to help clarify inheritance of variants identified. Sequencing and analysis for SouthSeq is conducted at the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama (https://www.hudsonalpha.org/). Results of testing are disclosed to participants by genetic counselors or trained non-genetics providers who also facilitate sharing of results with the participants' medical care teams when appropriate. Further, participant families may choose to opt-into return of secondary findings identified in the proband, which focus on pathogenic and likely pathogenic variation identified within the current ACMG gene list.

  Study phs003537

• Germline Sequence Variation in Cancer Genes Among Rwandan Breast and Prostate Cancer Cases

  Inherited genetic information can reduce cancer risk and mortality using protocols for patient ascertainment, testing, counseling, prevention, and treatment. For example, carriers of germline BRCA1/BRCA2 or Lynch Syndrome mutations are at increased risk of breast, ovarian, prostate, endometrial, colorectal, and other cancers. Genetic testing is of clinical value because many mutations are actionable in reducing risk or determining appropriate treatment regimens. There is growing evidence that inherited genetic mutations represent a large proportion of cancer cases in sub-Saharan Africa (SSA). It is also well known that most cancer genetic testing data does not represent the racial and ethnic diversity of the US or global population. Despite the high proportion of cancer cases diagnosed at an early age and late stage, as well as the potential for interventions to reduce cancer risk and death by using genetic tools, genetic testing, counseling, and clinical management protocols have largely not been widely developed in SSA. In order to develop and evaluate the potential for genetic testing in SSA, we propose to undertake a proof of concept feasibility study of hereditary cancer that will contribute data on the prevalence of hereditary cancer mutations in SSA and inform the development of SSA-specific guidelines for cancer genetic testing. In this study, we undertook a pilot evaluation of research genetic testing and counseling in breast and prostate cancer cases in Rwanda that involved genetic testing of breast and prostate cancer cases.

  Study phs003927

• National Cancer Institute Multi-Ancestry Genome-Wide Association Study of Kidney Cancer (NCI-3)

  The National Cancer Institute (NCI) multi-ancestral genome-wide association study (GWAS) of kidney cancer ("NCI-3") was performed by NCI to further investigate common genetic variants associated with risk of kidney cancer and its two major subtypes across individuals of different ancestries (European, African, East Asian, Latin American). The NCI-3 GWAS includes 12,315 cases and 73,091 controls from 25 centers in North America, South America and Europe, genotyped using the Illumina Global Screening Array v2.0. SNP-level results from this GWAS were combined by meta-analysis with results from two earlier NCI European-ancestry GWAS (RCC; phs000351: 1,311 cases and 3,424 controls and phs001736: 2,417 cases and 4,391 controls), a NCI GWAS of African Americans (phs000863; 255 cases and 375 controls), GWAS conducted at other institutions [International Agency for Research on Cancer (scan 1: 2,438 cases and 5,071 controls; scan 2: 2,781 cases and 2,940 controls), The University of Texas MD Anderson Cancer Center (scan 1: 893 cases and 556 controls, scan 2: 1,241 cases and 1,712 controls) and the Institute for Cancer Research, UK (944 cases and 4,024 controls)] and GWAS analyses of data from three large biobanks (Biobank Japan: 523 cases and 86,306 controls; FinnGen: 2,095 cases and 304,956 controls; UK Biobank: 1,807 cases and 348,824 controls). Only individual-level data from NCI-3 and the two MD Anderson Cancer Center scans are included in this dbGaP submission. All study-specific and meta-analysis summary statistics are included.

  Study phs003505

• Genetic Analysis of Epidermal Inclusion Cysts

  The goal of this study was to identify a potential driver of epidermal inclusion cysts, or epidermoid cysts, (EICs) in human skin. Individuals were recruited at EIC excision appointments made a priori, with no exclusion criteria. Fresh biopsies and saliva were taken from consented patients, and DNA harvested immediately. Whole exome sequencing was performed (150-bp paired end reads) to 200X in tissue and 80X in saliva via Illumina NovaSeq 6000 sequencer. Identification of somatic mutations was performed using GATK best practices. Somatic variants in the NEK9 gene were found in 12/14 cases sequenced, with clustering of variants within the RCC1 and kinase domains of the protein.

  Study phs003776

• Multi-Ethnic Study of Atherosclerosis (MESA) - Cardiac CT Image Repository

  The Multi-Ethnic Study of Atherosclerosis (MESA) is a study of the characteristics of subclinical cardiovascular disease (disease detected non-invasively before it has produced clinical signs and symptoms) and the risk factors that predict progression to clinically overt cardiovascular disease or progression of the subclinical disease. MESA researchers study a diverse, population-based sample of 6,814 asymptomatic men and women aged 45-84. Thirty-eight percent of the recruited participants are white, 28 percent African-American, 22 percent Hispanic, and 12 percent Asian, predominantly of Chinese descent. Data available for request include raw cardiac CT images. These new data are intended to be made available to interested researchers via BioData Catalyst, will include participants irrespective of participation in genetics (i.e. the full MESA cohort), and may be merged with currently posted (to dbGaP) phenotype and molecular datasets (WGS, GWA, RNA Seq, Methylation, Metabolomics, and Proteomics).

  Study phs004423

• Genome-Wide Association Study for Glucocorticoid-Induced Ocular Hypertension

  We aim to identify genetic variants associated with glucocorticoid (GC)-induced intraocular pressure (IOP) change utilizing genome-wide association study (GWAS) and whole exome sequencing (WES) analyses. The primary outcome was IOP change from baseline to the maximum IOP measurement within 6 months of GC treatment. Study participants were derived from two cohorts: the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) clinical trial and Massachusetts Eye and Ear Infirmary and Retina Health Center (MEE/RHC) clinical sites. The discovery analysis was conducted using the FAME samples (GWAS: n=532, WES: n=534) and replication analysis was done using the MEE/RHC samples (GWAS: n=603, WES: n=601).IOP was measured at baseline and throughout the first 6 months of GC exposure. DNA samples were collected through blood and underwent genome-wide genotyping on Illumina's Global Screening Array (GSA) and WES using a custom exome bait from TWIST Biosciences on the Agilent Bravo automated platform. Rare variant gene burden analyses were applied across all ancestries and in the European subgroup after adjusting for covariates. Gene-level and pathway analyses were performed using MAGMA and expression/splicing quantitative trait loci (eQTL/sQTL) colocalization was completed using eCAVIAR.Demographic and phenotypic information of the 1166 participants enrolled are available in this dbGaP deposition, including information on the GC medications, IOP measurements within the 6 month follow up period, and ocular hypertension/glaucoma history. Array derived genotypes, genotype calls derived from sequencing, and whole exome sequencing data will also be available.

  Study phs004037

• Kids First: Whole Genome Sequencing Studies of Multiplex Nonsyndromic Cleft Lip/Palate Families

  Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect that affects approximately 135,000 newborns worldwide, and imposes significant medical, psychosocial and financial burdens to affected individuals and their families. Genetic variation in numerous genes has been associated with NSCLP, however the exact mechanisms by which they contribute to the condition remain largely unknown. Here, we will use whole genome sequencing and robust analytical approaches to systematically evaluate the causes of NSCLP in 923 individuals from large multigenerational families.

  Study phs002626

• Incidental Detection of Maternal Neoplasia through Non-Invasive Cell-Free DNA Analysis (IDENTIFY), a Natural History Study

  Prenatal cell-free (cf) DNA sequencing for fetal aneuploidy incidentally detects circulating tumor DNA in the plasma of asymptomatic pregnant women. Distinguishing the subset of women with malignant tumors detected by prenatal sequencing from those with benign conditions, such as uterine fibroids, is critical to maternal medical management. The Incidental Detection of Maternal Neoplasia Through Non-Invasive Cell-Free DNA Sequencing (IDENTIFY) study at the National Institutes of Health in Bethesda, MD, offers standardized cancer screening and cfDNA sequencing to asymptomatic or minimally symptomatic pregnant women with nonreportable prenatal cfDNA sequencing results. We previously reported that whole-body magnetic resonance imaging (WB-MRI) and a specific genome-wide sequencing pattern of chromosomal gains and losses involving three or more chromosomes could reliably differentiate which women had cancer. We continue to explore additional noninvasive biomarkers to identify the subset of women with nonreportable prenatal cfDNA sequencing results who have cancer and to predict tissues of origin, particularly when patients or their providers are reluctant to pursue diagnostic testing, WB-MRI studies are unavailable, or imaging findings are indeterminate. Here, cfDNA sequence analysis was performed to identify cancer driver somatic mutations that might aid in distinguishing between pregnant women who have a high likelihood of occult malignancy from those who do not. In this pilot study, prospectively collected blood samples from 65 pregnant or postpartum women with and without occult cancers were analyzed blindly for cfDNA somatic mutations in 275 cancer-associated genes.

  Study phs004107

• Single Cell and Spatial Transcriptomics Studies of Fibrosis in Prospective Registry in IBD Study at MGH and GI Disease and Endoscopy Registry

  Stricturing disease or fibrosis is a common complication of inflammatory bowel disease (IBD), often requiring surgical intervention. This process is caused by the abnormal deposition of extracellular matrix in the context of inflammation, and thus involves crosstalk between multiple cell types including fibroblasts and immune cells. To understand the cellular interactions involved in fibrosis, we performed single cell and spatial transcriptomic analyses of biopsy or resection samples from IBD patients, diverticulitis patients or controls.For single cell analyses, intestinal samples were processed within three hours of collection by first stripping the epithelial layer with EDTA and then enzymatically digesting the underlying tissue. Cells from both the epithelial and tissue fractions were separately loaded in two channels on a 10x Chromium controller and libraries were generated with the 3'v3 Chemistry pipeline before sequencing on an Illumina sequencer. The resulting sequence data was demultiplexed and analyzed with the CellRanger pipeline to generate raw fastq files and processed gene-count matrices for each sample.For spatial transcriptomic analyses, intestinal resection samples were snap frozen in OCT (optimal cutting temperature embedding medium). Blocks were cut into 10μm sections in a cryostat and transferred to a 10x Genomics Visium slide v1. Spatially barcoded libraries were prepared according to manufacturer's instructions and sequencing on an Illumina sequencer. The resulting sequence data was processed with the SpaceRanger pipeline to generate fastq files and processed barcode-count matrices. Using the samples deposited here, we defined 68 fine-grained cell types across the ileum and colon of control and fibrotic intestinal tissues. We show that intestinal strictures were characterized by increased immune cells - including IgG+ plasma cells and CCR7hiCD4+ T cells - and inflammatory fibroblasts. We also define the transcriptional differences associated with fibrosis, with inflammatory fibroblasts in particular showing broad changes in gene expression. Spatial transcriptomics showed that key subsets colocalize within diseased tissues and identified additional populations such as interstitial cells of Cajal and enteric neurons. Further, we mapped gene expression onto intestinal biogeography, finding that known genetic risk loci are enriched within discrete spatial modules, defined by the presence of inflammatory fibroblasts and lymphoid follicles. Altogether, our datasets chart the key transcriptomic and cellular networks in stricturing CD and highlight the spatial organization of multicellular genetic risk factors.

  Study phs003943

• Non-Dependent Opioid Misusers as Controls for a Genome-Wide Association Study

  The Non-Dependent Opioid Misusers as GWAS Controls (i.e., the Opioid Misuse Study) is a genetic association study that was designed to compare adults with limited (6 months of daily or near daily) of opioid misuse. Participants were required to provide a source of DNA and to be of either non-Hispanic European American or African American ancestry (to yield adequately powered subsamples for genetic analyses). Adults (age >18 years) with a history of opioid misuse were recruited from Washington University School of Medicine (WUSM) recruitment and clinical sources, treatment centers, recovery residences, print and electronic advertisements, and social media. A brief, non-diagnostic screening call was completed to confirm the opioid misuse history of prospective participants. Limited lifetime misusers were required to have no opioid misuse for the past year. Extensive misusers were required to have had a clinical opioid use disorder diagnosis. Informed consent was obtained from all participants as per protocols approved by the institutional review boards of WUSM and the State of Missouri.A modified Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) obtained age of first, and most recent, use as well as DSM-5 substance use disorder diagnoses for heroin and prescription opioids (separately), cannabis, amphetamines, sedatives, cocaine, alcohol, and nicotine. Other assessed diagnoses included major depressive disorder, conduct disorder, and post-traumatic stress disorder. Non-diagnostic sections obtained information on demographics and suicidality. A short form version of the Addition Research Center Interview, added to assess the subjective effects of opioid misuse, was modified to enable retrospective assessment. A subsequent change to telephone interviews enabled recruitment of participants from a much broader geographic area encompassing the U.S. and Canada. Data are included here from 1774 individuals with a lifetime history of opioid misuse, of whom 1227 were of European American ancestry and 547 were of African American ancestry. We provide participants' estimated totals for number of times misused opioids lifetime and endorsement of opioid use disorder symptoms, which did not entirely correspond to our initial conceptualization of case and exposed control status.

  Study phs003684

• Integrative Analysis for Multi-Omics Data in Non-Small-Cell Lung Cancer

  We conducted epigenetic and transcriptomic mapping of primary non-small cell lung tumors and non-neoplastic tissues. 20 non-neoplastic lung tissues and 18 non-small cell lung tumors were obtained from Biorepository and Tissue Technology Shared Resource at Moores Cancer Center, UC San Diego. All tumor samples were in pathological stages I and II. 8 pairs of samples were "matched", meaning that the tumor and normal tissues came from the same patient. Microfluidic oscillatory washing–based chromatin immunoprecipitation followed by sequencing (MOWChIP-seq) was used to profile the binding of H3K4me1, H3K4me3, H3K9me3, H3K27ac and H3K27me3. SmartSeq-2 was used to map mRNA expression. We identified a large number of differentially modified regions for both epigenetic and transcriptomic markers between tumors and normal tissues. Deep learning model showed extensive transcription factor network rewiring. Raw sequencing data of the ChIP-seq and RNA-seq libraries are available through this dbGaP submission.

  Study phs003113

• Chicago Infant Mortality Study

  The Chicago Infant Mortality Study (CIMS) was a population-based, prospective, case-control study conducted in metropolitan Chicago, Cook County, Illinois, to examine the risk factors for sudden infant death syndrome (SIDS) among a primarily Black population. Eligible case infants were aged birth to one year where the cause of death was determined to be SIDS while eligible control infants were aged one month to one year who died of other sudden unexpected infant death (SUID) causes. Recruitment occurred between November 1993 and April 1996. The goal of this ancillary multiomics study was to evaluate possible genetic and epigenetic determinates of SIDS and together with metabolomic profiles, identify novel clinical diagnostic tools to enable molecular autopsies and biomarkers to proactively identify and intervene in infants at greater risk of death from SIDS. The multiomics data was generated from medical examiner autopsy specimens and includes: whole exome sequencing genotypes; RNA-seq transcriptome and methylome profiles from autopsy heart tissue; and serum metabolomics profiles. The sample size available varies with the modality of the omics assay, but the total number of unique infants included is about 400.

  Study phs003790

• Kids First: Genomic Analysis of Pediatric Rhabdomyosarcoma

  The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). All of the genomic and phenotypic data from this study are accessible through dbGaP. The data is also available at the Kids First Portal, where other Kids First datasets can also be accessed in the cloud for data analysis, data visualization, collaboration and interoperability, open to all researchers and developers. Rhabdomyosarcoma (RMS) is one of the most common and deadly sarcomas in children and adolescents, but very little is known about its genetic epidemiology. This study will explore the role of new (i.e., de novo) mutations in both known cancer predisposition genes and novel susceptibility genes on the risk of RMS. A better understanding of the genetic risks for RMS may lead to prevention strategies, better risk stratification, and even the identification of new therapeutic targets.

  Study phs004306

• Detecting and Subtyping Lung Cancer Through Analysis of Circulating Tumor DNA

  Small cell lung cancer (SCLC) is among the most aggressive tumors with poor clinical outcomes. Tumors are rarely resected, which is a major barrier to molecular profiling of tumor tissue; therefore, non-invasive approaches using circulating tumor DNA (ctDNA) from liquid biopsies are needed to help advance research and clinical care for patients with SCLC. We developed a targeted capture panel that profiles SCLC genes and transcriptional regulation sites, including transcription start sites (TSS) and transcription factor binding sites (TFBS). This is a single assay that detects genomic mutations and transcriptional regulation activity based on ctDNA fragment patterns reflecting epigenetic nucleosomal positions. We applied this assay to sequence patient-derived xenograft (PDX) and patient plasma samples. We also performed whole genome sequencing (WGS) for a subset of the PDX plasma samples to validate the capture data. We developed new algorithms to quantify activity of key SCLC marker genes of ASCL1, NEUROD1, POU2F3, and ATOH1 and to classify SCLC subtypes based on activity of these markers. Furthermore, we developed a model to classify SCLC from non-small cell lung cancer (NSCLC), which has potential important applications for monitoring transdifferentiation and tumor plasticity.

  Study phs003570

• Parkinson Cell Atlas in 5D (PD5D)

  Genome-wide association studies (GWAS) have unequivocally linked thousands of noncoding variants to Parkinson's disease (PD). Why have these breakthroughs not uncovered the mechanism(s) of common, genetically complex PD? We do not know how GWAS variants cause neurodegeneration, which variants are causal, and why they impair some brain cells but not others. Overwhelming evidence shows that cis regulation of transcription is the most likely mediator of disease risk, and that it is finely tuned by cellular and dynamic context.Here we will pinpoint the causal gene(s) through which GWAS loci function in spatially barcoded, single brain cells and, dynamically over pseudotime (Stage) using single-nucleus expression Quantitative Trait Locus (eQTL) analysis. Putative causal genes will be tested mechanistically in cell- and stage-specific analyses in vivo in Drosophila avatars and in vitro in human pluripotent stem cells. Moreover, we will identify the corresponding causal GWAS variants (eSNP) through allele-specific expression (ASE) and CRISPR/Cas9-variant editing in single brain cells. Our collaborative and highly integrated project will begin to reveal the complex human genetics of PD through a dynamic five-dimensional view of proximal cellular mechanisms across brain cells (1D), brain space (3D), and disease stage (1D).

  Study phs004421

• NCTN: Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome (AAML1531)

  Study ID: AAML1531 NCT Number: NCT02521493 Children's Oncology Group (COG) Submitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome (AAML1531) Trial Description: This phase III trial studies response-based chemotherapy in treating newly diagnosed acute myeloid leukemia or myelodysplastic syndrome in younger patients with Down syndrome. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Response-based chemotherapy separates patients into different risk groups and treats them according to how they respond to the first course of treatment (Induction I). Response-based treatment may be effective in treating acute myeloid leukemia or myelodysplastic syndrome in younger patients with Down syndrome while reducing the side effects. Clinical data presented in the following publication(s): • PMID 34320162 Disease type(s): • Hematopoietic Neoplasm/Leukemia - Acute Myeloid Leukemia • Hematopoietic Neoplasm/Leukemia - Myelodysplastic Syndrome Clinical Dataset(s) included:• NCT02521493-D1 (PMID 34320162): There are 2 datasets associated with PMID 34320162, NCT02521493-D1 through NCT02521493-D2. The NCT02521493-D1 dataset is a patient level dataset (single row per patient) containing patient characteristics, laboratory findings (hemoglobin, peripheral WBC, peripheral platelet), cytogenetics, outcome (overall survival and event-free survival), neutrophil recovery, ICU admission, select toxicity data, and targeted sequencing data for eligible myeloid leukemia in children with Down syndrome (ML-DS) enrolled on the AAML1531 clinical trial. • NCT02521493-D2 (PMID 34320162): There are 2 datasets associated with PMID 34320162, NCT02521493-D1 through NCT02521493-D2. The NCT02521493-D2 dataset is an adverse event level dataset (single row per adverse event, period, and patient) containing information of the micro-organisms associated with adverse events by period in the AAML1531 clinical trial. Additional genomic data are available for this trial under phs002187.You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

  Study phs004081

• National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from GenTAC include Aorta Tissue, Buffy Coat, DNA, EBV Cell Line, Lymphocytes, Plasma, and Polymorphonuclear Cells/RBC Pellets. Please note that use of biospecimens in genetic research is subject to a tiered consent. Objectives: The overall objective of GenTAC was to establish a registry of patients with genetically induced thoracic aortic aneurysms and related cardiovascular conditions, and collect associated medical data, as well as blood and tissue samples and make them available to investigators to advance research in diagnosis and management of genetically induced thoracic aortic aneurysms.Background: Thoracic aortic aneurysms (TAAs) predispose individuals to life threatening aortic complications, including aortic dissection and rupture. The treatment of complications arising from TAAs is complex, with high rates of morbidity, mortality, and surgical procedures. TAAs are associated with loss of vascular smooth muscle cells and degeneration of extracellular matrix in the aortic wall. This degeneration may be caused by hypertension and inflammation, particularly in elderly individuals. Genetic mutations are the main cause of TAAs in many young or middle-aged individuals. Genetic disorders, such as Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome, have a high risk for TAA, and up to 20% of individuals with TAAs or dissection have a family history of TAAs without being affected by a known syndrome or known genetic mutation. While diagnostic and treatment advances have dramatically improved care for patients with genetically induced TAAs, many questions remain about how best to identify and treat these disorders. Thus, GenTAC was developed as a longitudinal registry for patients affected by genetically induced thoracic aortic conditions in order to facilitate ongoing and future investigations to improve the diagnosis and clinical management of patients with genetically induced TAAs. Information gained from studying the genetically induced TAAs is expected to benefit the clinical management of non-genetic TAAs, as well.Participants: Over 3,500 participants were enrolled.Design: GenTAC was a longitudinal observational cohort study of affected individuals with either known or suspected genetic mutation that predisposes them for thoracic aortic aneurysms and dissections (TAAD). There were no interventions planned, and all decisions regarding approaches to treatment were to be made by the patients and their care teams. Enrollment data were abstracted from medical records or obtained through patient interviews. The data collected include clinical evaluations (by several organ systems), historically diagnosed conditions and outcomes and drug treatment; patient reported quality of life, co-morbidities, family history, smoking, alcohol use, and pregnancy history; most recent imaging evaluations, genetic testing, blood chemistry, and surgical interventions. When blood could not be collected from participants, a saliva sample was obtained as a source of DNA. Excess aortic tissue was frozen from participants that underwent surgery. Follow-up data was collected at regular intervals for each participant enrolled, with the interval varying by the diagnosis. Follow-up data include outcomes, clinical and imaging evaluations and treatment and lifestyle changes since the enrollment visit. Images were read by the imaging core according to the study protocol. Diagnosis of each participant was confirmed by the phenotyping core.Conclusions: GenTAC established a vast biospecimen inventory and clinical database from over 3500 participants that is available to researchers with the ultimate goal of advancing the diagnosis and management of genetically induced thoracic aortic aneurysms and other cardiovascular complications. Some of the publications resulting from analysis of the GenTAC data and biospecimens can be found at https://www.nhlbi.nih.gov/research/resources/gentac/research.Publications: A list of GenTAC publications can be found on the GenTAC Alliance website: https://www.gentacalliance.org/publications/.

  Study phs004340

• Genome-Wide Association Study and Predictors of Neonatal Blood Cell Traits in Hispanic Newborns

  This study leverages cord blood samples from the NHLBI's Umbilical Cord Blood Unit Collection to conduct genome-wide association studies (GWAS) of neonatal blood cell traits in newborns of Hispanic ethnicity. Cord blood (CB) aliquots from 382 de-identified newborns of Hispanic ethnicity were obtained from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) through Project Request #11595. The CB samples were originally collected between 1998-2001 as part of the COBLT (Cord Blood Transplantation) study. Briefly, the COBLT study primarily aimed to (i) build ethnically diverse public cord blood banks with standardized collection/processing protocols and (ii) to conduct a prospective phase II trial of unrelated cord-blood transplantation in pediatric and adult candidates for allogeneic hematopoietic stem cell transplantation. The collected CB units and aliquots are currently maintained by BioLINCC, with samples available from donors with diverse racial/ethnic background. All COBLT CB samples were red cell depleted, volume reduced and cryopreserved with DMSO/Dextran in 25 ml bags. Test aliquots were used by COBLT for flow cytometry to characterize predictors of time to engraftment for CB samples. Cell surface markers assessed included CD34, CD45, CD3, CD8, CD4, CD19, CD16, and CD56. CB aliquots were requested from subjects reported as Hispanic in the NHLBI Umbilical Cord Blood Unit Collection. Epidemiological data and cell-related indices were obtained from the Umbilical Cord Blood Unit Collection repository. To investigate genetic variation associated with blood cell traits measured in the Hispanic newborn samples, we isolated DNA from CB and conducted genome-wide SNP genotyping using the Axiom PangenomiX array (Thermo Fisher). Whole-genome imputation was performed using the TOPMed Imputation Server, and GWAS of 24 blood and immune cell traits were conducted in up to 382 Hispanic newborns for each trait.

  Study phs004758

• Health Effects of Arsenic Longitudinal Study

  The Health Effects of Arsenic Longitudinal Study (HEALS), a multidisciplinary and large prospective cohort study in Araihazar, Bangladesh, was established to evaluate the effects of full-dose range arsenic (As) exposure on various health outcomes. We applied array-based genotyping technologies to baseline DNA samples from a subset of the HEALS study and linked those genotypes to data on arsenic species measured in urine. We used these data to identify regions influencing arsenic metabolism (AS3MT and FTCD). We also applied array-based DNA methylation technologies to baseline DNA samples from a subset of individuals from HEALS. These data were linked to data on arsenic concentration (in both urine and drinking water) to identify regions of the genome where DNA methylation is impacted by arsenic exposure.

  Study phs003839

• Blood and Marrow Clinical Trials Network - A Multi-Center, Phase III, Randomized Trial of RIC, and Transplantation of (dUCB) Versus HLA-Haplo Related Bone Marrow for Patients with Hematologic Malignancies (BMT CTN-1101-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.ObjectivesTo compare double unrelated umbilical cord blood and HLA-mismatched (haploidentical) related donor transplantations for the treatment of leukemia and lymphoma in adults.BackgroundEarlier studies have shown that partially HLA-mismatched related bone marrow (haplo-BM) and unrelated double umbilical cord blood (dUCB) are valuable sources of donor cells for Reduced-Intensity Conditioning (RIC) hematopoietic cell transplants (HCT) in patients that do not have access to either an HLA-matched sibling or suitably HLA-matched unrelated donor. Both haplo-BM and dUCB grafts are more accessible for patients lacking an HLA-matched donor.This study assessed the hypothesis that progression-free survival at two years after haplo-BM transplantation is similar to the progression-free survival after dUCB transplantation.ParticipantsPatients aged 18 to 70 years with chemotherapy-sensitive lymphoma or acute leukemia in remission were assigned to undergo double unrelated umbilical cord blood (n = 186) or HLA-mismatched (haploidentical) related donor transplantation (n = 182). Of the 186 patients randomized to the dUCB arm, 172 received the treatment as assigned. Of the 182 patients randomized to the haplo-BM arm, 153 received the treatment as assigned.Enrolled patients had a Karnofsky score greater than or equal to 70% and adequate physical function of the cardiac, hepatic, renal, and pulmonary systems. Furthermore, subjects had one of the following: Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR); Acute Myelogenous Leukemia (AML) in CR1; Acute Leukemias in 2nd or subsequent CR; Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR; adult T-cell leukemia/lymphoma in first or subsequent CR; Burkitt's lymphoma: second or subsequent CR; chemotherapy-sensitive Lymphoma.DesignParticipants were enrolled in the study between June of 2012 and June 2018 and randomized 1:1 using random block sizes stratified by transplant centers (n=33). The primary end point was 2-year progression-free survival (PFS).The donor and recipient in the haplo-BM arm were HLA identical for at least one antigen (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1.Patients enrolled in the dUCB arm had to have two UCB units with a minimum of 1.5 x 10^7/kg pre-cryopreserved total nucleated cell dose. For non-red blood cell depleted units, the minimum pre-cryopreserved total nucleated cell dose of each unit was at least 2.0 x10^7/kg. Furthermore, units were HLA matched at a minimum of 4/6 to the recipient at HLA -A, HLA-B (at low resolution using DNA based typing), and HLA -DRB1 (at high resolution using DNA based typing).All participants received a conditioning regimen/preparative regimen prior to transplant as well as a GVHD prophylaxis regimen.Participants randomized to the dUCB arm received the following conditioning regimen: fludarabine cyclophosphamide, and either 200 or 300 cGy total-body irradiation (TBI). GVHD prophylaxis started 3 days prior to transplantation and included 15 mg/kg mycophenolate mofetil three times daily (with a maximum daily dose of 3 g) through day 35 and cyclosporine adjusted to maintain a trough level of 200 to 400 ng/mL through day 100 and tapered by 10% weekly until discontinued between days 180 and 200.Participants randomized to the haplo-BM received the following conditioning regimen: cyclophosphamide, fludarabine, and 200 cGy TBI. GVHD prophylaxis consisted of 50 mg/kg cyclophosphamide IV daily on days 3 and 4, 15 mg/kg mycophenolate mofetil three times daily from days 5 through 35, and tacrolimus adjusted to maintain a concentration of 5 to 15 ng/mL from day 5 through day 180.ConclusionsThere were no significant differences seen in progression-free survival between double unrelated umbilical cord blood and HLA-mismatched (haploidentical) related donor transplantations for leukemia or lymphoma. Analyses of secondary end points, including overall survival, favored haploidentical BM donors.Fuchs EJ, O'Donnell PV, Eapen M, et al. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood. 2021;137(3):420-428. doi:10.1182/blood.2020007535

  Study phs004698

• Lung Cancer Genetic Study Among Asian Never Smokers

  The Lung Cancer Genetic Study Among Asian Never Smokers includes data from four population-based studies conducted among Asian women: the Shanghai Women's Health Study (SWHS), the Hwasun Cancer Epidemiology Study (HCES1 and HCES2), the Female Lung Cancer Consortium in Asia (FLCCA, including sFLCA), and the Guangzhou Lung Cancer Study (GLCS). Shanghai Women's Health Study (SWHS): The SWHS is a population-based prospective cohort study of approximately 75,000 adult women who were recruited between 1997 and 2000. The cohort has been followed by a combination of record linkage and active follow-ups. Lung cancer patients identified in the SWHS and non-cases were included in the current study.Hwasun Cancer Epidemiology Study-Lung Cancer (HCES1 and HCES2): The HCES is a hospital-based case-control study whose goal is to identify factors of the cancer development and clinical progression in a Korean population. Included in this project were 299 female lung cancer cases from HCES2, who were diagnosed between April 2004 and February 2013 at Chonnam National University Hwasun Hospital, a cancer specified hospital in Jeollanam-do province, South Korea. Controls were randomly selected from women with no previous cancer diagnosis at enrollment in the Namwon Study and the Dong-gu study, ongoing community-based cohort studies in South Korea. A total of 1,103 controls (273 from HCES1 and 830 from HCES2) were genotyped by MEGA. Guangzhou Lung Cancer Study (GLCS): The GLCS is a case-control study including never-smoking women lung cancer cases and controls from Guangzhou, China.In this study, the DNA samples of 1,195 subjects from SWHS and GLCS were genotyped using whole exome sequencing (WES), and the DNA samples of 7,174 subjects from SWHS, HCES1, HCES2, FLCCA, and sFLCA were genotyped using the Multi-Ethnic Global Array (MEGA).

  Study phs002366

• Multi-Omics Study of Lung Cancer in Smokers From EAGLE

  EAGLE (Environment And Genetics in Lung cancer Etiology) is a population-based case-control study examining the full spectrum of lung cancer etiology from smoking initiation, smoking dependency to lung cancer development and outcome. It combines a traditional molecular epidemiology design with more integrative approaches by examining epidemiological, molecular, and clinical data together. To comprehensively investigate the effect of tobacco smoking behaviors on genomic or epigenomic alterations, we performed a multi-omics study including whole-genomic, transcriptomic, and epigenomic profiles in a total of 221 individuals from the EAGLE study.

  Study phs002992

• SCORCH: Revealing the Single Cell Determinants of Brain Relevant to Persistent HIV Infection and Opioid Use Disorder

  People living with HIV (PLWH) are at the higher risk for impaired cognitive functions such as HIV-Associated Neurocognitive Disorder or HAND. Further, higher use of legal and illegal opioids among PLWH could affect their immune functions and exacerbate CNS impairment. However, little is known about the HIV harboring cell types in brain, effect of ART on specific CNS cell types, and the modification of brain functions by opioid use. The human brain is composed of an enormous diversity of cell types defined by distinct gene expression, morphology, connectivity, and physiology. Single cell sequencing assays enable cell type-specific analysis of the role of these cell types in healthy brain function and disease. The overall objective of this proposal is to reveal the single cell determinants of opioid use disorder in the brain relevant to persistent HIV infection using snRNA-seq and snATAC-seq technologies, bioinformatics approaches, and validation studies. Single cell and spatial characterization of HIV and opioid use disorder across multiple regions of the human brain will be performed. These regions may include nucleus accumbens (NAc), prefrontal cortex (PFC), cerebellum, amygdala, and other accessible regions. These results will provide an unprecedented conceptual and experimental system to identify single cell determinants of opioid use disorder in the brain relevant to persistent HIV infection as well as potential opportunities to illuminate how genetic variation affects gene expression.

  Study phs004026