Exploiting the GTEx resources to decipher the mechanisms at GWAS loci
Top Cited Papers
Open Access
- 26 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Genome Biology
- Vol. 22 (1), 1-24
- https://doi.org/10.1186/s13059-020-02252-4
Abstract
The resources generated by the GTEx consortium offer unprecedented opportunities to advance our understanding of the biology of human diseases. Here, we present an in-depth examination of the phenotypic consequences of transcriptome regulation and a blueprint for the functional interpretation of genome-wide association study-discovered loci. Across a broad set of complex traits and diseases, we demonstrate widespread dose-dependent effects of RNA expression and splicing. We develop a data-driven framework to benchmark methods that prioritize causal genes and find no single approach outperforms the combination of multiple approaches. Using colocalization and association approaches that take into account the observed allelic heterogeneity of gene expression, we propose potential target genes for 47% (2519 out of 5385) of the GWAS loci examined.Funding Information
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK20595)
- National Institute of Health (R01MH107666)
This publication has 57 references indexed in Scilit:
- Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study dataNature Biotechnology, 2013
- Validating therapeutic targets through human geneticsNature Reviews Drug Discovery, 2013
- Recent Explosive Human Population Growth Has Resulted in an Excess of Rare Genetic VariantsScience, 2012
- Clan Genomics and the Complex Architecture of Human DiseaseCell, 2011
- Trait-Associated SNPs Are More Likely to Be eQTLs: Annotation to Enhance Discovery from GWASPLoS Genetics, 2010
- Apolipoprotein B and Cardiovascular Disease Risk: Position Statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best PracticesClinical Chemistry, 2009
- Cholesterol and non-cholesterol sterol transporters: ABCG5, ABCG8 and NPC1L1: a reviewXenobiotica, 2008
- Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disordersNucleic Acids Research, 2004
- High-level expression of ABCG5 and ABCG8 attenuates diet-induced hypercholesterolemia and atherosclerosis in Ldlr−− miceJournal of Lipid Research, 2004
- Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretionProceedings of the National Academy of Sciences, 2002