Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-07

AUTHORS

Eric R. Gamazon, Ayellet V. Segrè, Martijn van de Bunt, Xiaoquan Wen, Hualin S. Xi, Farhad Hormozdiari, Halit Ongen, Anuar Konkashbaev, Eske M. Derks, François Aguet, Jie Quan, , Dan L. Nicolae, Eleazar Eskin, Manolis Kellis, Gad Getz, Mark I. McCarthy, Emmanouil T. Dermitzakis, Nancy J. Cox, Kristin G. Ardlie

ABSTRACT

We apply integrative approaches to expression quantitative loci (eQTLs) from 44 tissues from the Genotype-Tissue Expression project and genome-wide association study data. About 60% of known trait-associated loci are in linkage disequilibrium with a cis-eQTL, over half of which were not found in previous large-scale whole blood studies. Applying polygenic analyses to metabolic, cardiovascular, anthropometric, autoimmune, and neurodegenerative traits, we find that eQTLs are significantly enriched for trait associations in relevant pathogenic tissues and explain a substantial proportion of the heritability (40-80%). For most traits, tissue-shared eQTLs underlie a greater proportion of trait associations, although tissue-specific eQTLs have a greater contribution to some traits, such as blood pressure. By integrating information from biological pathways with eQTL target genes and applying a gene-based approach, we validate previously implicated causal genes and pathways, and propose new variant and gene associations for several complex traits, which we replicate in the UK BioBank and BioVU. More... »

PAGES

956-967

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41588-018-0154-4

DOI

http://dx.doi.org/10.1038/s41588-018-0154-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105156420

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29955180


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