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Nature DOI:10.1038/nature13005

Detection and replication of epistasis influencing transcription in humans.

Publication TypeJournal Article
Year of Publication2014
AuthorsHemani, G, Shakhbazov, K, Westra, H-J, Esko, T, Henders, AK, McRae, AF, Yang, J, Gibson, G, Martin, NG, Metspalu, A, Franke, L, Montgomery, GW, Visscher, PM, Powell, JE
JournalNature
Volume508
Issue7495
Pages249-53
Date Published2014 Apr 10
ISSN1476-4687
KeywordsCohort Studies, Epistasis, Genetic, Europe, Female, Gene Expression Profiling, Gene Expression Regulation, Genetic Association Studies, Humans, Linkage Disequilibrium, Male, Pedigree, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results, Transcription, Genetic
Abstract

Epistasis is the phenomenon whereby one polymorphism's effect on a trait depends on other polymorphisms present in the genome. The extent to which epistasis influences complex traits and contributes to their variation is a fundamental question in evolution and human genetics. Although often demonstrated in artificial gene manipulation studies in model organisms, and some examples have been reported in other species, few examples exist for epistasis among natural polymorphisms in human traits. Its absence from empirical findings may simply be due to low incidence in the genetic control of complex traits, but an alternative view is that it has previously been too technically challenging to detect owing to statistical and computational issues. Here we show, using advanced computation and a gene expression study design, that many instances of epistasis are found between common single nucleotide polymorphisms (SNPs). In a cohort of 846 individuals with 7,339 gene expression levels measured in peripheral blood, we found 501 significant pairwise interactions between common SNPs influencing the expression of 238 genes (P 

URLhttp://dx.doi.org/10.1038/nature13005
DOI10.1038/nature13005
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24572353?dopt=Abstract

Alternate JournalNature
PubMed ID24572353
PubMed Central IDPMC3984375
Grant ListR01 AA007535 / AA / NIAAA NIH HHS / United States
R01 AA014041 / AA / NIAAA NIH HHS / United States
AA13320 / AA / NIAAA NIH HHS / United States
GM099568 / GM / NIGMS NIH HHS / United States
DA12854 / DA / NIDA NIH HHS / United States
P01 GM099568 / GM / NIGMS NIH HHS / United States
AA13321 / AA / NIAAA NIH HHS / United States
AA10248 / AA / NIAAA NIH HHS / United States
R01 AA013326 / AA / NIAAA NIH HHS / United States
R56 DA012854 / DA / NIDA NIH HHS / United States
R01 AA013321 / AA / NIAAA NIH HHS / United States
GM057091 / GM / NIGMS NIH HHS / United States
R01 DA012854 / DA / NIDA NIH HHS / United States
AA014041 / AA / NIAAA NIH HHS / United States
R01 GM075091 / GM / NIGMS NIH HHS / United States
AA13326 / AA / NIAAA NIH HHS / United States
R01 AA013320 / AA / NIAAA NIH HHS / United States