International Consortium for Blood Pressure GWAS 2011 discovery dataset
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA189296 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:International Consortium for Blood Pressure GWAS 2011 discovery dataset
| PRJNA189396 | ENA
Project description:<p>The ICBP consortium is an international effort to investigate blood-pressure genetics. The consortium was formed by two parent consortia, the CHARGE-BP consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology - blood pressure) and the GBPGEN consortium (Global Blood Pressure Genetics Consortium).</p> <p>In 2011 we performed genome-wide association analyses based on genome-wide SNPs imputed to HapMap for systolic and diastolic blood pressure (SBP and DBP) and mean arterial pressure and pulse pressure (MAP and PP).</p> <p>In 2016 we performed an analysis based on the Cardio-MetaboChip for SBP and DBP.</p> <p>All these datasets are available here, however, full association statistics including effect size directions, only under controlled access by dbGaP.</p>
| phs000585 | dbGaP
Project description:NEI NEIGHBOR Consortium Glaucoma GWAS
| PRJNA75557 | ENA
Project description:International Parkinson's Disease Consortium (IPDGC), NeuroX Dataset
| PRJNA284551 | ENA
Project description:NIDDK IBD Genetics Consortium Ulcerative Colitis GWAS
| PRJNA75853 | ENA
Project description:A robust system using disease relevant cells to systematically evaluate the role in diabetes for loci identified through genome wide association studies (GWAS) is urgently needed. Toward this goal, we created isogenic mutant human embryonic stem cell (hESC) lines in GWAS-identified candidate diabetes genes including CDKAL1, KCNQ1 and KCNJ11, and used directed differentiation to evaluate the function of derivative human beta-like cells. The mutations did not affect the generation of insulin+ cells, but impaired insulin secretion both in vitro and in vivo, coinciding with defective glucose homeostasis. CDKAL1-/- insulin+ cells also displayed hypersensitivity to lipotoxicity. A high-content chemical screen identified a candidate drug that rescued CDKAL1-/--specific defects by inhibiting the AP1 (FOS/JUN) pathway. These studies establish a platform using isogenic hESCs to evaluate the function of GWAS-identified loci, and identify a drug candidate that rescues gene-specific defects, paving the way to precision therapy of metabolic diseases.A robust system using disease relevant cells to systematically evaluate the role in diabetes for loci identified through genome wide association studies (GWAS) is urgently needed. Toward this goal, we created isogenic mutant human embryonic stem cell (hESC) lines in GWAS-identified candidate diabetes genes including CDKAL1, KCNQ1 and KCNJ11, and used directed differentiation to evaluate the function of derivative human beta-like cells. The mutations did not affect the generation of insulin+ cells, but impaired insulin secretion both in vitro and in vivo, coinciding with defective glucose homeostasis. CDKAL1-/- insulin+ cells also displayed hypersensitivity to lipotoxicity. A high-content chemical screen identified a candidate drug that rescued CDKAL1-/--specific defects by inhibiting the AP1 (FOS/JUN) pathway. These studies establish a platform using isogenic hESCs to evaluate the function of GWAS-identified loci, and identify a drug candidate that rescues gene-specific defects, paving the way to precision therapy of metabolic diseases.
2016-07-12 | GSE76308 | GEO
Project description:NIDDK International IBD Genetics Consortium Repository Global Screening Array
| PRJNA695808 | ENA
Project description:NIDDK International IBD Genetics Consortium Repository Global Screening Array
| PRJNA695809 | ENA
Project description:The EVE Asthma Genetics Consortium: Building Upon GWAS
| PRJNA326562 | ENA
Project description:Genome-wide association studies (GWAS) have identified blood pressure-related loci, but functional insights into causality and related molecular mechanisms lag behind. We functionally characterize 4608 genetic variants in linkage with blood pressure loci in vascular smooth muscle cells (VSMCs) and cardiomyocytes (CMs) by massively parallel reporter assays (MPRAs). Regulatory variants are in non-conserved loci, enriched in repeats, and alter trait-relevant transcription factor binding sites. Higher-order genome organization indicates that loci harboring regulatory variants converge in spatial hubs to control specific signaling pathways required for proper cardiovascular function. Modelling different variant allele frequencies by CRISPR prime editing led to expression changes of KCNK9, SFXN2, and PCGF6. We provide mechanistic insights into how regulatory variants converge their effects on blood pressure genes (i.e. ULK4, MAP4, CFDP1, PDE5A, 10q24.32), and cardiovascular pathways. Our findings support advances in molecular precision medicine to define functionally relevant variants and the genetic architecture of blood pressure genes.
2023-04-25 | GSE213558 | GEO