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

Elin Grundberg; Kerrin S. Small; Asa K. Hedman; Alexandra C. Nica; Alfonso Buil; Sarah Keildson; Jordana T. Bell; Tsun-Po Yang; Eshwar Meduri; Amy Barrett; James Nisbett; Magdalena Sekowska; Alicja Wilk; So-Youn Shin; Daniel Glass; Mary Travers; Josine L. Min; Sue Ring; Karen Ho; Gudmar Thorleifsson; Augustine Kong; Unnur Thorsteindottir; Chrysanthi Ainali; Antigone S. Dimas; Neelam Hassanali; Catherine Ingle; David Knowles; Maria Krestyaninova; Christopher E. Lowe; Paola Di Meglio; Stephen B. Montgomery; Leopold Parts; Simon Potter; Gabriela Surdulescu; Loukia Tsaprouni; Sophia Tsoka; Veronique Bataille; Richard Durbin; Frank O. Nestle; Stephen O'Rahilly; Nicole Soranzo; Cecilia M. Lindgren; Krina T. Zondervan; Kourosh R. Ahmadi; Eric E. Schadt; Kari Stefansson; George Davey Smith; Mark I. McCarthy; Panos Deloukas; Emmanouil T. Dermitzakis; Tim D. Spector; Multiple Tissue Human Expression R

doi:10.1038/ng.2394

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

Journal article

Peer reviewed

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

Elin Grundberg, Kerrin S. Small, Asa K. Hedman, Alexandra C. Nica, Alfonso Buil, Sarah Keildson, Jordana T. Bell, Tsun-Po Yang, Eshwar Meduri, Amy Barrett, …

Nature genetics, Vol.44(10), pp.1084-1089

01/10/2012

DOI: https://doi.org/10.1038/ng.2394

PMCID: PMC3784328

PMID: 22941192

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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.

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Title: Mapping cis- and trans-regulatory effects across multiple tissues in twins
Creators - without role: Elin Grundberg - Wellcome Sanger Institute
Kerrin S. Small - Wellcome Sanger Institute
Asa K. Hedman - University of Oxford
Alexandra C. Nica - University of Geneva
Alfonso Buil - University of Geneva
Sarah Keildson - University of Oxford
Jordana T. Bell - University of Oxford
Tsun-Po Yang - Wellcome Sanger Institute
Eshwar Meduri - Wellcome Sanger Institute
Amy Barrett - University of Oxford
James Nisbett - Wellcome Sanger Institute
Magdalena Sekowska - Wellcome Sanger Institute
Alicja Wilk - Wellcome Sanger Institute
So-Youn Shin - Wellcome Sanger Institute
Daniel Glass - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Mary Travers - University of Oxford
Josine L. Min - University of Oxford
Sue Ring - University of Bristol
Karen Ho - University of Bristol
Gudmar Thorleifsson - deCODE Genet, Reykjavik, Iceland
Augustine Kong - deCODE Genet, Reykjavik, Iceland
Unnur Thorsteindottir - deCODE Genet, Reykjavik, Iceland
Chrysanthi Ainali - Supreme Council Of Health
Antigone S. Dimas - University of Geneva
Neelam Hassanali - University of Oxford
Catherine Ingle - Wellcome Sanger Institute
David Knowles - University of Cambridge
Maria Krestyaninova - European Bioinformat Inst, Hinxton, England
Christopher E. Lowe - University of Cambridge
Paola Di Meglio - Kings Coll London, St Johns Inst Dermatol, London WC2R 2LS, England
Stephen B. Montgomery - University of Geneva
Leopold Parts - Wellcome Sanger Institute
Simon Potter - Wellcome Sanger Institute
Gabriela Surdulescu - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Loukia Tsaprouni - Wellcome Sanger Institute
Sophia Tsoka - Supreme Council Of Health
Veronique Bataille - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Richard Durbin - Wellcome Sanger Institute
Frank O. Nestle - Kings Coll London, St Johns Inst Dermatol, London WC2R 2LS, England
Stephen O'Rahilly - University of Cambridge
Nicole Soranzo - Wellcome Sanger Institute
Cecilia M. Lindgren - University of Oxford
Krina T. Zondervan - University of Oxford
Kourosh R. Ahmadi - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Eric E. Schadt - Supreme Council Of Health
Kari Stefansson - deCODE Genet, Reykjavik, Iceland
George Davey Smith - University of Bristol
Mark I. McCarthy - University of Oxford
Panos Deloukas - Wellcome Sanger Institute
Emmanouil T. Dermitzakis - University of Geneva
Tim D. Spector - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Multiple Tissue Human Expression R
Publication Details: Nature genetics, Vol.44(10), pp.1084-1089
Publisher: Springer Nature
Number of pages: 8
Grant note: Swiss National Science Foundation; Swiss National Science Foundation (SNSF) NCCR Frontiers in Genetics; Swiss National Science Foundation (SNSF) European Community's Seventh Framework Programme (FP7); European Commission G0900339 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 090532 / core funding for the Wellcome Trust Centre for Human Genetics; Wellcome Trust Louis-Jeantet Foundation 081917/Z/07/Z / program grant from the Wellcome Trust; Wellcome Trust ENGAGE project; General Electric G0600698B; G0600717B; G0900339; G9815508 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) US National Institutes of Health-NIMH grant (GTEx project); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Identifiers: 9937350608331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article