<title>Author Summary</title>
<p>Regulation of gene expression is a fundamental cellular process determining a large proportion of the phenotypic variance. Previous studies have identified genetic loci influencing gene expression levels (eQTLs), but the complexity of their tissue-specific properties has not yet been well-characterized. In this study, we perform <italic>cis</italic>-eQTL analysis in a unique matched co-twin design for three human tissues derived simultaneously from the same set of individuals. The study design allows validation of the substantial discoveries we make in each tissue. We explore in depth the tissue-dependent features of regulatory variants and estimate the proportions of shared and specific effects. We use continuous measures of eQTL sharing to circumvent the statistical power limitations of comparing direct overlap of eQTLs in multiple tissues. In this framework, we demonstrate that 30% of eQTLs are shared among tissues, while 29% are exclusively tissue-specific. Furthermore, we show that the fold change in expression between eQTL genotypic classes differs between tissues. Even among shared eQTLs, we report a substantial proportion (10%–20%) of significant tissue differences in magnitude of these effects. The complexities we highlight here are essential for understanding the impact of regulatory variants on complex traits.</p>
Description
PLOS Genetics: The Architecture of Gene Regulatory Variation across Multiple Human Tissues: The MuTHER Study
%0 Journal Article
%1 nica2011architecture
%A Nica, Alexandra C.
%A Parts, Leopold
%A Glass, Daniel
%A Nisbet, James
%A Barrett, Amy
%A Sekowska, Magdalena
%A Travers, Mary
%A Potter, Simon
%A Grundberg, Elin
%A Small, Kerrin
%A Hedman, Åsa K.
%A Bataille, Veronique
%A Tzenova Bell, Jordana
%A Surdulescu, Gabriela
%A Dimas, Antigone S.
%A Ingle, Catherine
%A Nestle, Frank O.
%A di Meglio, Paola
%A Min, Josine L.
%A Wilk, Alicja
%A Hammond, Christopher J.
%A Hassanali, Neelam
%A Yang, Tsun-Po
%A Montgomery, Stephen B.
%A O'Rahilly, Steve
%A Lindgren, Cecilia M.
%A Zondervan, Krina T.
%A Soranzo, Nicole
%A Barroso, Inês
%A Durbin, Richard
%A Ahmadi, Kourosh
%A Deloukas, Panos
%A McCarthy, Mark I.
%A Dermitzakis, Emmanouil T.
%A Spector, Timothy D.
%A Consortium, The MuTHER
%D 2011
%I Public Library of Science
%J PLoS Genet
%K Tissue-specific
%N 2
%P e1002003
%R 10.1371/journal.pgen.1002003
%T The Architecture of Gene Regulatory Variation across Multiple Human Tissues: The MuTHER Study
%U http://dx.doi.org/10.1371%2Fjournal.pgen.1002003
%V 7
%X <title>Author Summary</title>
<p>Regulation of gene expression is a fundamental cellular process determining a large proportion of the phenotypic variance. Previous studies have identified genetic loci influencing gene expression levels (eQTLs), but the complexity of their tissue-specific properties has not yet been well-characterized. In this study, we perform <italic>cis</italic>-eQTL analysis in a unique matched co-twin design for three human tissues derived simultaneously from the same set of individuals. The study design allows validation of the substantial discoveries we make in each tissue. We explore in depth the tissue-dependent features of regulatory variants and estimate the proportions of shared and specific effects. We use continuous measures of eQTL sharing to circumvent the statistical power limitations of comparing direct overlap of eQTLs in multiple tissues. In this framework, we demonstrate that 30% of eQTLs are shared among tissues, while 29% are exclusively tissue-specific. Furthermore, we show that the fold change in expression between eQTL genotypic classes differs between tissues. Even among shared eQTLs, we report a substantial proportion (10%–20%) of significant tissue differences in magnitude of these effects. The complexities we highlight here are essential for understanding the impact of regulatory variants on complex traits.</p>
@article{nica2011architecture,
abstract = { <title>Author Summary</title>
<p>Regulation of gene expression is a fundamental cellular process determining a large proportion of the phenotypic variance. Previous studies have identified genetic loci influencing gene expression levels (eQTLs), but the complexity of their tissue-specific properties has not yet been well-characterized. In this study, we perform <italic>cis</italic>-eQTL analysis in a unique matched co-twin design for three human tissues derived simultaneously from the same set of individuals. The study design allows validation of the substantial discoveries we make in each tissue. We explore in depth the tissue-dependent features of regulatory variants and estimate the proportions of shared and specific effects. We use continuous measures of eQTL sharing to circumvent the statistical power limitations of comparing direct overlap of eQTLs in multiple tissues. In this framework, we demonstrate that 30% of eQTLs are shared among tissues, while 29% are exclusively tissue-specific. Furthermore, we show that the fold change in expression between eQTL genotypic classes differs between tissues. Even among shared eQTLs, we report a substantial proportion (10%–20%) of significant tissue differences in magnitude of these effects. The complexities we highlight here are essential for understanding the impact of regulatory variants on complex traits.</p>
},
added-at = {2014-11-12T22:52:45.000+0100},
author = {Nica, Alexandra C. and Parts, Leopold and Glass, Daniel and Nisbet, James and Barrett, Amy and Sekowska, Magdalena and Travers, Mary and Potter, Simon and Grundberg, Elin and Small, Kerrin and Hedman, Åsa K. and Bataille, Veronique and Tzenova Bell, Jordana and Surdulescu, Gabriela and Dimas, Antigone S. and Ingle, Catherine and Nestle, Frank O. and di Meglio, Paola and Min, Josine L. and Wilk, Alicja and Hammond, Christopher J. and Hassanali, Neelam and Yang, Tsun-Po and Montgomery, Stephen B. and O'Rahilly, Steve and Lindgren, Cecilia M. and Zondervan, Krina T. and Soranzo, Nicole and Barroso, Inês and Durbin, Richard and Ahmadi, Kourosh and Deloukas, Panos and McCarthy, Mark I. and Dermitzakis, Emmanouil T. and Spector, Timothy D. and Consortium, The MuTHER},
biburl = {https://www.bibsonomy.org/bibtex/2b8774521abaa4083ea1b8e21d3378533/sfb23},
description = {PLOS Genetics: The Architecture of Gene Regulatory Variation across Multiple Human Tissues: The MuTHER Study},
doi = {10.1371/journal.pgen.1002003},
interhash = {4dfa7efcfbfe5334efbd8440f0dfd655},
intrahash = {b8774521abaa4083ea1b8e21d3378533},
journal = {PLoS Genet},
keywords = {Tissue-specific},
month = {02},
number = 2,
pages = {e1002003},
publisher = {Public Library of Science},
timestamp = {2014-11-12T22:54:30.000+0100},
title = {The Architecture of Gene Regulatory Variation across Multiple Human Tissues: The MuTHER Study},
url = {http://dx.doi.org/10.1371%2Fjournal.pgen.1002003},
volume = 7,
year = 2011
}