3613 results for "*geneti*"

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• 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