Item type: | Article | ||||
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Journal or Publication Title: | The American Journal of Human Genetics | ||||
Publisher: | CELL PRESS | ||||
Place of Publication: | CAMBRIDGE | ||||
Volume: | 109 | ||||
Number of Issue or Book Chapter: | 8 | ||||
Page Range: | pp. 1366-1387 | ||||
Date: | 2022 | ||||
Institutions: | Medicine > Abteilung für Nephrologie Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie | ||||
Identification Number: |
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Keywords: | INTEGRATIVE ANALYSIS; WIDE ASSOCIATION; 3D GENOME; VARIANTS; CHOLESTEROL; ANNOTATION; OBESITY; COMMON; LOCI; EXPRESSION; | ||||
Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
Status: | Published | ||||
Refereed: | Yes, this version has been refereed | ||||
Created at the University of Regensburg: | Partially | ||||
Item ID: | 57818 |
Abstract
A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with ...
Abstract
A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
Metadata last modified: 28 Jun 2024 04:25