Exploiting the GTEx resources to decipher the mechanisms at GWAS loci-Reference-Cited by-同舟云学术

Exploiting the GTEx resources to decipher the mechanisms at GWAS loci

Published:2021-01-26 Issue:1 Volume:22 Page:
ISSN:1474-760X
Container-title:Genome Biology
language:en
Short-container-title:Genome Biol

Author:

Barbeira Alvaro N., ,Bonazzola Rodrigo,Gamazon Eric R.,Liang Yanyu,Park YoSon,Kim-Hellmuth Sarah,Wang Gao,Jiang Zhuoxun,Zhou Dan,Hormozdiari Farhad,Liu Boxiang,Rao Abhiram,Hamel Andrew R.,Pividori Milton D.,Aguet François,Bastarache Lisa,Jordan Daniel M.,Verbanck Marie,Do Ron,Stephens Matthew,Ardlie Kristin,McCarthy Mark,Montgomery Stephen B.,Segrè Ayellet V.,Brown Christopher D.,Lappalainen Tuuli,Wen Xiaoquan,Im Hae Kyung^ORCID,

Abstract

AbstractThe 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.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Health

Publisher

Springer Science and Business Media LLC

Link

http://link.springer.com/content/pdf/10.1186/s13059-020-02252-4.pdf

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