3613 results for "*geneti*"

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• Pharmacogenomics of Statin Therapy (POST)

  A central goal of the Pharmacogenomics of Statin Therapy (POST) study was to identify genetic and other factors that contribute to the clinical efficacy and adverse effects of statins. Approximately 700 Kaiser Permanente of Northern California (KPNC) members who were current or former statin users were recruited as POST participants based on their electronic health record (EHR) data. Some participants experienced myocardial infarction while on statins, developed dysglycemia while on statins, and/or had myopathy symptoms while on statins, while the remainder were “unaffected” statin-treated controls. Genotype array data was generated from almost all POST participants, and induced pluripotent stem cells (iPSCs) were created for a subset of POST participants for in vitro statin exposures and transcriptomic analysis.

  Study phs003596

• African American Cardiovascular Pharmacogenomics Consortium (ACCOuNT)

  The African American Cardiovascular Pharmacogenomics Consortium (ACCOuNT) assembled an observational cohort to characterize genetic and clinical determinants of inter‑individual variability in warfarin dose requirements among participants of African ancestry receiving anticoagulation care. The submission includes individual‑level genotypes in PLINK format (.bed/.bim/.fam) and a harmonized phenotype file with stable warfarin dose, age, height, weight, and concomitant medication indicators (aspirin, amiodarone) for 309 participants. Biospecimens are germline DNA from peripheral blood; no tumor samples and no case–control disease labels are involved. The resource is intended to enable discovery and validation of pharmacogenomic loci, development of dose‑prediction models, and methods benchmarking focused on underrepresented populations. Data available through dbGaP comprise the genotype files, the subject‑level phenotype dataset, and minimal sample metadata needed to link subjects to biospecimens.

  Study phs004279

• Identification of Modifiers of 22q11.2 Deletion Syndrome in Whole Genome Sequence - CIDR

  This project aims to identify genetic modifiers of congenital heart disease (CHD), which occurs among 22q11.2 deletion syndrome (22q11.2DS; also known as DiGeorge syndrome/velo-cardio-facial syndrome) patients. In contrast to the prevalence of ~0.8% in the general population, about 60%-70% of 22q11.2DS patients have CHD, of which most are conotruncal heart defects, making 22q11.2DS a very ideal model to study the genetic underpins of CHD. The chromosome 22q11.2 region is susceptible to meiotic chromosome rearrangements leading to hemizygous deletions, because there are large blocks of low copy repeats, termed LCR22s, that are dispersed in the region. Non-allelic homologous recombination during meiosis can lead to specific-sized deletions. Approximately 90% have a typical hemizygous 3 million base pair (Mb) deletion between LCR22-A and -D, while some have nested deletions between LCR22-A and B or LCR22-A and C. Our goal is to perform a case-control association study, in which cases have CHD, while controls have normal heart structures, all with 22q11.2DS. All individuals are unrelated and have been collected from collaborators in the US, Canada and Europe. All subjects received a clinical diagnosis of 22q11.2DS and signed informed consent to allow a blood sample to be collected for research. The DNA samples were de-identified in 2 steps to protect their privacy. We then determined deletion type using multiplex ligation-dependent probe amplification (MLPA). This information is provided for the great majority of subjects. We also obtained cardiac phenotype information from echocardiogram reports as well as reported race and ethnicity (Hispanic vs. non-Hispanic information), which is required for the analysis. We will obtain 30X whole-genome sequence data from NIH CIDR. We will first annotate the sequence variants identified to uncover rare ( For genotype data, we will provide the raw fastq data from whole-genome sequencing as well as the called variants file in a VCF file. For phenotype data, we will provide the sample relationship files (ped files), CHD affection status, deletion type, and race.

  Study phs002514

• Brain and Genetic Predictors of Placebo Analgesia

  Design: Observational, population twin-based cohort study conducted at the University of Colorado, Boulder. Primary Aim: To investigate how genetics and brain function jointly influence individual differences in pain perception and placebo response, using thermal and mechanical experimental pain protocols and measuring neural responses via fMRI.Outcome Measures: Pain ratings on a Visual Analog Scale (VAS) from 0 (no pain) to 100 (most intense pain imaginable) during pain tasks. These ratings were taken during a single four-hour experimental session. Phenotypic data is shared for 460 individuals, and genotypic data is shared for 247 of the 460 individuals.Data from this study are also available from OpenNeuro.org.

  Study phs002118

• Genetic Basis of Early Onset Bicuspid Aortic Valve Disease

  The study protocol was approved by the Committee for the Protection of Human Subjects at the University of Texas Health Science Center at Houston (HSC-MS-11-0185). Study recruitment began on July 1, 2017, and concluded on March 30, 2022. After written informed consent, we enrolled probands with early onset BAV disease (EBAV), which we defined as individuals with BAV who were under the age of 30 at the time of first clinical event. Clinical events were defined as aortic replacement, aortic valve surgery, aortic dissection, moderate or severe aortic stenosis or aortic regurgitation, large aneurysm (Z > 4.5), or intervention for BAV-related conditions. Those with hypoplastic left heart, known genetic mutations, genetic syndromes, or complex congenital heart disease were excluded. Samples were collected and genotyped as previously reported. For comparison, we analyzed a cohort of older individuals of European ancestry with sporadic BAV disease selected from the International BAV Consortium (BAVGWAS). Phenotypes were derived from record review with confirmation of image data whenever possible [25-26]. The computational pipeline for CNV analysis of Illumina single nucleotide polymorphism (SNP) array data included three independent CNV detection algorithms.GenomeStudio was used to exclude samples with indeterminate sex or more than 5% missing genotypes, and single nucleotide polymorphisms (SNPs) with GenTrain = 0. Principal component analysis was used to remove outliers that did not cluster with European ancestry. Prior to CNV analysis, each dataset was trimmed by selecting a common set of 650,000 SNPs that were genotyped on each of the microarrays used in this study.Three independent algorithms (PennCNV, cnvPartition, and QuantiSNP) were used to generate CNV calls and sample-level quality statistics from SNP intensity data. PennCNV and QuantiSNP were run on Unix clusters and cnvPartition data were exported from GenomeStudio. The analysis was run using default configurations. PennCNV was used to generate QC data and remove CNV calls that intersect with polymorphic genomic regions. Samples that met any of the following criteria were excluded, standard deviation of the LogR ratio (obtained from PennCNV) > 0.35 or number of CNVs > 2 standard deviations above the mean for each data set. CNV calls less than 20 Kilobases in length and/or spanned by fewer than 6 probes were excluded. The overlap function for rare CNVs in PLINK was used to construct CNV regions (CNVRs) after adjacent regions were merged using PennCNV. LogR ratio (LRR) and B allele frequency (BAF) data at CNVRs and calls of interest were visualized in GenomeStudio for validation. For segregation analysis, GenomeStudio was used to determine the presence of CNVs in relatives.A total of 22,014 unselected control Illumina Genotypes obtained from the Database of Genotypes and Phenotypes were analyzed using identical methods (S1 Table). The Wisconsin Longitudinal Study (WLS) includes data on a cohort of 10,300 individuals who graduated from Wisconsin high schools in 1957. The Health and Retirement Study (HRS) includes data on 37,000 individuals aged 50 above from 23,000 households across the United States. Principal component analysis was used to select European ancestry genotypes from these datasets for analysis. Datasets were paired for case-control analysis based on the concordance of log-transformed sample-level quality control statistics (number of CNV calls and standard deviation of logR ratios). Chi-squared or Fisher exact tests were used to compare CNV frequencies in cases and controls.Rare CNV functions in PLINK (v1.7) were used to perform permutation-based burden tests or gene set-based enrichment tests. Case control burden tests were restricted to CNVs that were longer than 110 Kb and less than 0.1% in frequency. CNV overlap functions in PLINK were used to identify rare CNVs that intersect between datasets or involve specific BAV or CHD genes . The list of candidate genes included 190 CHD genes that have strong cumulative evidence to cause BAV or related congenital malformations from human or animal model data. Genome Reference Consortium Human Build 37 was used for CNV annotation [34].

  Study phs003705

• Whole Exome Sequencing of PCOS

  Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women of reproductive age and is characterized by hyperandrogenism, oligomenorrhea/amenorrhea, and polycystic ovaries. The goals of this project were to 1) generate a comprehensive catalog of likely causal PCOS associated variants, 2) establish the functional consequences of the genetic variants identified by whole exome sequencing (WES) using bioinformatic and molecular strategy, and 3) identify genes and molecular pathways that are genetically impaired in PCOS with the goal of providing more targeted treatment for PCOS. To achieve these goals, we carried out WES on a total of 1064 samples corresponding to 1049 unique subjects (15 subjects had duplicate sequencing samples). The samples include 731 PCOS cases (731 unique), 318 controls (309 controls), and 15 samples of unknown phenotype (6 PPCOSII, 9 HapMap controls). Controls are reproductive age women with normal androgens and regular menses as phenotype control. We designed a Custom WES array which includes the standard CIDR WES array plus 9.8 Mb of Twist Custom Design added content encoding genomic regions in linkage disequilibrium with PCOS associated GWAS regions. Sequencing was performed at the Center for Inherited Disease Research (CIDR), Johns Hopkins University School of Medicine. Target templates are sequenced to >100x coverage using paired-end reads on the Illumina NovaSeq6000 platform.

  Study phs004025

• DNA Termini Correlate with Methylation at CpG Sites in Hair, Urine and Blood Plasma Cell-Free DNA

  The aim of this study was to reconstruct the age of individuals from cell-free DNA (cfDNA) present in rootless hair and urine samples using epigenetic clock methods. Hair was chosen as a noninvasive source for biological age estimation and a sample type which is relevant in forensic science. Samples were obtained from anonymous volunteers. The study expands epigenetic clock research to hair tissue and provides a resource for modeling age-related changes in CpG methylation. Whole genome shotgun sequencing data was generated for all samples using a single-stranded library preparation.

  Study phs004104

• Association Between Telomere Length and Falciparum Malaria Endemicity in Sub-Saharan Africans

  The goal of this study was to identify the genetic and environmental drivers of telomere length variation in an ethnically diverse African cohort. It comprises 1,818 participants from Cameroon, Tanzania, Ethiopia, and Botswana. For each participant, leukocyte telomere length was measured using the Southern blotting of the terminal restriction fragment methodology. 1,758 of the individuals with phenotype data also had genetic data, and these individuals were subjected to a genome-wide association study which accounted for age, sex, and genetic relatedness. Individuals were genotyped on one of two genotyping arrays (Illumina Infinium Omni5 array or Illumina H3Africa consortium array). Genetic datasets were merged, and missing genotypes were imputed for a final genetic dataset of 11,001,107 genetic variants. Correlations between telomere length and a variety of environmental factors, including malaria endemicity, were also examined in this study.

  Study phs003567

• Epigenetic Damage in Women Living in LA Food-Desert Zip Codes

  This study investigated the impact of insulin resistance on chromatin acetylation and inflammation. Blood samples were obtained from women consented to City of Hope Institutional Review Board (IRB)-approved COH Protocol#/Ref#:18306/158149. Women provided demographic information and completed a survey assessing diet, housing and medical history. BMI was obtained from medical records. HgbA1c was measured and cytokine arrays were used to measure serum TNFalpha, IL6, IL15, IL16, IL23, Leptin, and CXCL1.

  Study phs003522

• A genotype-phenotype study of tumors from patients with inherited mutations in DNA repair genes

  This study investigated the genomic landscape of tumors from patients with inherited mutations in DNA repair genes. The aim of this study was to determine the relationship between locus-specific loss of heterozygosity (LOH) and genomic signatures of homologous recombination-based DNA repair (HR) deficiency in tumors associated with pathogenic germline variants in DNA repair genes. Cohorts of pathogenic germline variant (PGV) carriers with different cancer types were identified via a cancer genetics registry and clinical practice at Penn Medicine and through our collaborator network. Tumors were analyzed with next generation sequencing (whole exome and/or targeted panel sequencing) with or without transcriptomic analyses. Sub-study #1 "Non-breast/ovarian tumors in germline BRCA1/2 carriers". This study investigated primary non-breast/ovarian tumors that arise in individuals with BRCA1/BRCA2 pathogenic germline variants (PGVs). Whole exome sequencing (WES) using Agilent All-Exon Kit v7 hybrid capture probes was performed on matched tumor and blood germline normal DNA on an Illumina HiSeq. Individual WES data from DNA samples from tumor and normal are available. Sub-study #2: "Breast tumors in germline CHEK2 carriers". This study investigated primary breast tumors that arise in individuals with CHEK2 pathogenic germline variants (PGVs). Whole exome sequencing (WES) using Agilent All-Exon Kit v7 hybrid capture probes was performed on matched tumor and blood germline normal DNA on an Illumina HiSeq. Whole transcriptome RNAseq was performed on tumors. Individual WES data from DNA samples from tumor and normal and RNAseq data from tumor are available. Sub-study #3: "Breast tumors in germline TP53 carriers". This study investigated primary breast tumors that arise in individuals with TP53 pathogenic germline variants (PGVs). Whole genome sequencing (WGS) and/or custom panel targeted sequencing was performed on matched tumor and blood germline normal DNA on an Illumina HiSeq. Whole transcriptome RNAseq was performed on tumors and normal breast tissue. Individual WGS or targeted data from DNA samples from tumor and normal and RNASeq data from tumor and normal are available. Sub-study #4: "Prostate tumors in germline DNA repair carriers". This study investigated prostate tumors that arise in individuals with a variety of pathogenic germline variants (PGVs). Whole genome sequencing (WGS) and/or custom panel targeted sequencing was performed on matched tumor and blood germline normal DNA on an Illumina HiSeq. Whole transcriptome RNAseq was performed on tumors and normal prostate tissue. Individual WGS or targeted data from DNA samples from tumor and normal and RNASeq data from tumor and normal are available.

  Study phs003348