Patterns of \(Cis\) Regulatory Variation in Diverse Human Populations

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Patterns of \(Cis\) Regulatory Variation in Diverse Human Populations

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dc.contributor.author Montgomery, Stephen B.
dc.contributor.author Dimas, Antigone S.
dc.contributor.author Parts, Leopold
dc.contributor.author Stegle, Oliver
dc.contributor.author Ingle, Catherine E.
dc.contributor.author Sekowska, Magda
dc.contributor.author Gutierrez-Arcelus, Maria
dc.contributor.author Nisbett, James
dc.contributor.author Nica, Alexandra C.
dc.contributor.author Beazley, Claude
dc.contributor.author Durbin, Richard
dc.contributor.author Deloukas, Panos
dc.contributor.author Dermitzakis, Emmanouil T.
dc.contributor.author Stranger, Barbara Elaine
dc.contributor.author Smith, George W.
dc.contributor.author Price, Alkes
dc.contributor.author Raj, Towfique
dc.date.accessioned 2012-10-26T15:28:09Z
dc.date.issued 2012
dc.identifier.citation Stranger, Barbara E., Stephen B. Montgomery, Antigone S. Dimas, Leopold Parts, Oliver Stegle, Catherine E. Ingle, Magda Sekowska, et al. 2012. Patterns of \(cis\) regulatory variation in diverse human populations. PLoS Genetics 8(4): e1002639. en_US
dc.identifier.issn 1553-7390 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:9807331
dc.description.abstract The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants, but also more recently to assist in the interpretation and elucidation of disease signals. To date, many studies have looked in specific tissues and population-based samples, but there has been limited assessment of the degree of inter-population variability in regulatory variation. We analyzed genome-wide gene expression in lymphoblastoid cell lines from a total of 726 individuals from 8 global populations from the HapMap3 project and correlated gene expression levels with HapMap3 SNPs located in \(cis\) to the genes. We describe the influence of ancestry on gene expression levels within and between these diverse human populations and uncover a non-negligible impact on global patterns of gene expression. We further dissect the specific functional pathways differentiated between populations. We also identify 5,691 expression quantitative trait loci (eQTLs) after controlling for both non-genetic factors and population admixture and observe that half of the \(cis\)-eQTLs are replicated in one or more of the populations. We highlight patterns of eQTL-sharing between populations, which are partially determined by population genetic relatedness, and discover significant sharing of eQTL effects between Asians, European-admixed, and African subpopulations. Specifically, we observe that both the effect size and the direction of effect for eQTLs are highly conserved across populations. We observe an increasing proximity of eQTLs toward the transcription start site as sharing of eQTLs among populations increases, highlighting that variants close to TSS have stronger effects and therefore are more likely to be detected across a wider panel of populations. Together these results offer a unique picture and resource of the degree of differentiation among human populations in functional regulatory variation and provide an estimate for the transferability of complex trait variants across populations. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pgen.1002639 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330104/pdf/ en_US
dash.license LAA
dc.subject biology en_US
dc.subject genetics en_US
dc.subject gene expression en_US
dc.subject human genetics en_US
dc.subject population genetics en_US
dc.subject genomics en_US
dc.title Patterns of \(Cis\) Regulatory Variation in Diverse Human Populations en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Genetics en_US
dash.depositing.author Stranger, Barbara Elaine
dc.date.available 2012-10-26T15:28:09Z

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