Detection and replication of epistasis influencing transcription in humans

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 dem...

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Bibliographic Details
Published in:Nature (London) 2014-04, Vol.508 (7495), p.249-253
Main Authors: Hemani, Gibran, Shakhbazov, Konstantin, Westra, Harm-Jan, Esko, Tonu, Henders, Anjali K, McRae, Allan F, Yang, Jian, Gibson, Greg, Martin, Nicholas G, Metspalu, Andres, Franke, Lude, Montgomery, Grant W, Visscher, Peter M, Powell, Joseph E
Format: Article
Language:English
Subjects:
Chromosomes
Cohort Studies
Epistasis, Genetic - genetics
Europe - ethnology
Expected values
Female
Gene expression
Gene Expression Profiling
Gene Expression Regulation - genetics
Genetic aspects
Genetic Association Studies
Genetic epistasis
Genetic polymorphisms
Genetic transcription
Genetics
Genotype & phenotype
Humans
Hypotheses
Linkage Disequilibrium
Male
Pedigree
Physiological aspects
Polymorphism
Polymorphism, Single Nucleotide - genetics
Quantitative Trait Loci
Reproducibility of Results
Transcription, Genetic - genetics
Online Access:Get full text
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Summary: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 
ISSN:0028-0836
1476-4687
DOI:10.1038/nature13005