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

Grundberg, E, Small, KS, Hedman, Å, Nica, AC, Buil, A, Keildson, S, Bell, JT, Yang, TP, Meduri, E, Barrett, A , Nisbett, J, Sekowska, M, Wilk, A, Shin, SY, Glass, D, Travers, M, Min, JL, Ring, S, Ho, K, Thorleifsson, G, Kong, A, Thorsteindottir, U, Ainali, C, Dimas, AS, Hassanali, N, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, CE, Di Meglio, P, Montgomery, SB, Parts, L, Potter, S, Surdulescu, G, Tsaprouni, L, Tsoka, S, Bataille, V, Durbin, R, Nestle, FO, O'Rahilly, S, Soranzo, N, Lindgren, CM, Zondervan, KT, Ahmadi, KR, Schadt, EE, Stefansson, K, Smith, GD, McCarthy, MI, Deloukas, P, Dermitzakis, ET, Spector, TD and Multiple Tissue Human Expression Resource (MuTHER) Consortium, (2012) Mapping cis- and trans-regulatory effects across multiple tissues in twins. Nat Genet, 44 (10). pp. 1084-1089.

Full text not available from this repository.

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.

Item Type: Article
Authors :
NameEmailORCID
Grundberg, EUNSPECIFIEDUNSPECIFIED
Small, KSUNSPECIFIEDUNSPECIFIED
Hedman, ÅUNSPECIFIEDUNSPECIFIED
Nica, ACUNSPECIFIEDUNSPECIFIED
Buil, AUNSPECIFIEDUNSPECIFIED
Keildson, SUNSPECIFIEDUNSPECIFIED
Bell, JTUNSPECIFIEDUNSPECIFIED
Yang, TPUNSPECIFIEDUNSPECIFIED
Meduri, EUNSPECIFIEDUNSPECIFIED
Barrett, AUNSPECIFIEDUNSPECIFIED
Nisbett, JUNSPECIFIEDUNSPECIFIED
Sekowska, MUNSPECIFIEDUNSPECIFIED
Wilk, AUNSPECIFIEDUNSPECIFIED
Shin, SYUNSPECIFIEDUNSPECIFIED
Glass, DUNSPECIFIEDUNSPECIFIED
Travers, MUNSPECIFIEDUNSPECIFIED
Min, JLUNSPECIFIEDUNSPECIFIED
Ring, SUNSPECIFIEDUNSPECIFIED
Ho, KUNSPECIFIEDUNSPECIFIED
Thorleifsson, GUNSPECIFIEDUNSPECIFIED
Kong, AUNSPECIFIEDUNSPECIFIED
Thorsteindottir, UUNSPECIFIEDUNSPECIFIED
Ainali, CUNSPECIFIEDUNSPECIFIED
Dimas, ASUNSPECIFIEDUNSPECIFIED
Hassanali, NUNSPECIFIEDUNSPECIFIED
Ingle, CUNSPECIFIEDUNSPECIFIED
Knowles, DUNSPECIFIEDUNSPECIFIED
Krestyaninova, MUNSPECIFIEDUNSPECIFIED
Lowe, CEUNSPECIFIEDUNSPECIFIED
Di Meglio, PUNSPECIFIEDUNSPECIFIED
Montgomery, SBUNSPECIFIEDUNSPECIFIED
Parts, LUNSPECIFIEDUNSPECIFIED
Potter, SUNSPECIFIEDUNSPECIFIED
Surdulescu, GUNSPECIFIEDUNSPECIFIED
Tsaprouni, LUNSPECIFIEDUNSPECIFIED
Tsoka, SUNSPECIFIEDUNSPECIFIED
Bataille, VUNSPECIFIEDUNSPECIFIED
Durbin, RUNSPECIFIEDUNSPECIFIED
Nestle, FOUNSPECIFIEDUNSPECIFIED
O'Rahilly, SUNSPECIFIEDUNSPECIFIED
Soranzo, NUNSPECIFIEDUNSPECIFIED
Lindgren, CMUNSPECIFIEDUNSPECIFIED
Zondervan, KTUNSPECIFIEDUNSPECIFIED
Ahmadi, KRk.ahmadi@surrey.ac.ukUNSPECIFIED
Schadt, EEUNSPECIFIEDUNSPECIFIED
Stefansson, KUNSPECIFIEDUNSPECIFIED
Smith, GDUNSPECIFIEDUNSPECIFIED
McCarthy, MIUNSPECIFIEDUNSPECIFIED
Deloukas, PUNSPECIFIEDUNSPECIFIED
Dermitzakis, ETUNSPECIFIEDUNSPECIFIED
Spector, TDUNSPECIFIEDUNSPECIFIED
Multiple Tissue Human Expression Resource (MuTHER) Consortium, UNSPECIFIEDUNSPECIFIED
Date : October 2012
Identification Number : 10.1038/ng.2394
Uncontrolled Keywords : Adult, Aged, Aged, 80 and over, Chromosome Mapping, Female, Gene Expression Regulation, Gene-Environment Interaction, Genetic Linkage, Humans, Lymphocytes, Middle Aged, Models, Genetic, Organ Specificity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Skin, Subcutaneous Fat, Transcription, Genetic
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:48
Last Modified : 17 May 2017 14:44
URI: http://epubs.surrey.ac.uk/id/eprint/825173

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