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

Nica, Alexandra; Buil Demur, Alfonso Alberto; Dima, Antigoni; Montgomery, Stephen; Dermitzakis, Emmanouil

doi:10.1038/ng.2394

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Title		Mapping cis- and trans-regulatory effects across multiple tissues in twins
Authors		Nica, Alexandra Buil Demur, Alfonso Alberto Dima, Antigoni Montgomery, Stephen Dermitzakis, Emmanouil
Published in		Nature genetics. 2012, vol. 44, no. 10, p. 1084-9
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.
Keywords		Adult — Aged — Aged, 80 and over — Chromosome Mapping — Female — Gene Expression Regulation — Gene-Environment Interaction — Genetic Linkage — Humans — Lymphocytes/metabolism — Middle Aged — Models, Genetic — Organ Specificity — Polymorphism, Single Nucleotide — Quantitative Trait Loci — Skin/metabolism — Subcutaneous Fat/metabolism — Transcription, Genetic
Identifiers		DOI: 10.1038/ng.2394 PMID: 22941192
Full text		Article (Published version) (535 Kb) - Free access
Structures		Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement
Research group		Population Genomics and Genetics of Complex Traits (892)
Project		Autre: Jeantet
Citation (ISO format)		NICA, Alexandra et al. Mapping cis- and trans-regulatory effects across multiple tissues in twins. In: Nature Genetics, 2012, vol. 44, n° 10, p. 1084-9. doi: 10.1038/ng.2394 https://archive-ouverte.unige.ch/unige:32156