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Mapping cis- and trans-regulatory effects across multiple tissues in twins.


ABSTRACT: Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many expression quantitative trait locus (eQTL) studies, typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression. Using identity-by-descent estimates, we show that at least 40% of the total heritable cis effect on expression cannot be accounted for by common cis variants, a finding that reveals the contribution of low-frequency and rare regulatory variants with respect to both transcriptional regulation and complex trait susceptibility. We show that a substantial proportion of gene expression heritability is trans to the structural gene, and we identify several replicating trans variants that act predominantly in a tissue-restricted manner and may regulate the transcription of many genes.

SUBMITTER: Grundberg E 

PROVIDER: S-EPMC3784328 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Mapping cis- and trans-regulatory effects across multiple tissues in twins.

Grundberg Elin E   Small Kerrin S KS   Hedman Åsa K ÅK   Nica Alexandra C AC   Buil Alfonso A   Keildson Sarah S   Bell Jordana T JT   Yang Tsun-Po TP   Meduri Eshwar E   Barrett Amy A   Nisbett James J   Sekowska Magdalena M   Wilk Alicja A   Shin So-Youn SY   Glass Daniel D   Travers Mary M   Min Josine L JL   Ring Sue S   Ho Karen K   Thorleifsson Gudmar G   Kong Augustine A   Thorsteindottir Unnur U   Ainali Chrysanthi C   Dimas Antigone S AS   Hassanali Neelam N   Ingle Catherine C   Knowles David D   Krestyaninova Maria M   Lowe Christopher E CE   Di Meglio Paola P   Montgomery Stephen B SB   Parts Leopold L   Potter Simon S   Surdulescu Gabriela G   Tsaprouni Loukia L   Tsoka Sophia S   Bataille Veronique V   Durbin Richard R   Nestle Frank O FO   O'Rahilly Stephen S   Soranzo Nicole N   Lindgren Cecilia M CM   Zondervan Krina T KT   Ahmadi Kourosh R KR   Schadt Eric E EE   Stefansson Kari K   Smith George Davey GD   McCarthy Mark I MI   Deloukas Panos P   Dermitzakis Emmanouil T ET   Spector Tim D TD  

Nature genetics 20120902 10


Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many expression quantitative trait locus (eQTL) studies, typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression. U  ...[more]

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