Mapping cis-and trans-regulatory effects across multiple tissues in twins
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Sprog: | English |
| Udgivet: |
2012
|
| _version_ | 1826277458016468992 |
|---|---|
| author | Grundberg, E Small, K Hedman, A Nica, A Buil, A Keildson, S Bell, J Yang, T Meduri, E Barrett, A Nisbett, J Sekowska, M Wilk, A Shin, S Glass, D Travers, M Min, J Ring, S Ho, K Thorleifsson, G Kong, A Thorsteindottir, U Ainali, C Dimas, A Hassanali, N |
| author_facet | Grundberg, E Small, K Hedman, A Nica, A Buil, A Keildson, S Bell, J Yang, T Meduri, E Barrett, A Nisbett, J Sekowska, M Wilk, A Shin, S Glass, D Travers, M Min, J Ring, S Ho, K Thorleifsson, G Kong, A Thorsteindottir, U Ainali, C Dimas, A Hassanali, N |
| author_sort | Grundberg, E |
| collection | OXFORD |
| description | 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. © 2012 Nature America, Inc. All rights reserved. |
| first_indexed | 2024-03-06T23:29:11Z |
| format | Journal article |
| id | oxford-uuid:6b6d45dd-af9b-44bc-9c88-aed0d052cc4c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:29:11Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:6b6d45dd-af9b-44bc-9c88-aed0d052cc4c2022-03-26T19:04:01ZMapping cis-and trans-regulatory effects across multiple tissues in twinsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6b6d45dd-af9b-44bc-9c88-aed0d052cc4cEnglishSymplectic Elements at Oxford2012Grundberg, ESmall, KHedman, ANica, ABuil, AKeildson, SBell, JYang, TMeduri, EBarrett, ANisbett, JSekowska, MWilk, AShin, SGlass, DTravers, MMin, JRing, SHo, KThorleifsson, GKong, AThorsteindottir, UAinali, CDimas, AHassanali, NSequence-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. © 2012 Nature America, Inc. All rights reserved. |
| spellingShingle | Grundberg, E Small, K Hedman, A Nica, A Buil, A Keildson, S Bell, J Yang, T Meduri, E Barrett, A Nisbett, J Sekowska, M Wilk, A Shin, S Glass, D Travers, M Min, J Ring, S Ho, K Thorleifsson, G Kong, A Thorsteindottir, U Ainali, C Dimas, A Hassanali, N Mapping cis-and trans-regulatory effects across multiple tissues in twins |
| title | Mapping cis-and trans-regulatory effects across multiple tissues in twins |
| title_full | Mapping cis-and trans-regulatory effects across multiple tissues in twins |
| title_fullStr | Mapping cis-and trans-regulatory effects across multiple tissues in twins |
| title_full_unstemmed | Mapping cis-and trans-regulatory effects across multiple tissues in twins |
| title_short | Mapping cis-and trans-regulatory effects across multiple tissues in twins |
| title_sort | mapping cis and trans regulatory effects across multiple tissues in twins |
| work_keys_str_mv | AT grundberge mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT smallk mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT hedmana mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT nicaa mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT buila mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT keildsons mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT bellj mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT yangt mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT medurie mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT barretta mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT nisbettj mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT sekowskam mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT wilka mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT shins mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT glassd mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT traversm mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT minj mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT rings mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT hok mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT thorleifssong mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT konga mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT thorsteindottiru mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT ainalic mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT dimasa mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins AT hassanalin mappingcisandtransregulatoryeffectsacrossmultipletissuesintwins |