Search: (WFRF:(Hassanali Neelam)) pers:(Spector Timothy D)
> (2011) >
The architecture of...
-
Nica, Alexandra C
(author)
The architecture of gene regulatory variation across multiple human tissues : the MuTHER study.
- Article/chapterEnglish2011
Publisher, publication year, extent ...
-
2011-02-03
-
Public Library of Science (PLoS),2011
-
printrdacarrier
Numbers
-
LIBRIS-ID:oai:DiVA.org:uu-275702
-
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-275702URI
-
https://doi.org/10.1371/journal.pgen.1002003DOI
Supplementary language notes
-
Language:English
-
Summary in:English
Part of subdatabase
Classification
-
Subject category:ref swepub-contenttype
-
Subject category:art swepub-publicationtype
Notes
-
While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples (156 LCL, 160 skin, 166 fat) were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes). In addition, we apply factor analysis (FA) to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes). The unique study design (Matched Co-Twin Analysis--MCTA) permits immediate replication of eQTLs using co-twins (93%-98%) and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%-20%) have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
-
Parts, Leopold
(author)
-
Glass, Daniel
(author)
-
Nisbet, James
(author)
-
Barrett, Amy
(author)
-
Sekowska, Magdalena
(author)
-
Travers, Mary
(author)
-
Potter, Simon
(author)
-
Grundberg, Elin
(author)
-
Small, Kerrin
(author)
-
Hedman, Asa K
(author)
-
Bataille, Veronique
(author)
-
Tzenova Bell, Jordana
(author)
-
Surdulescu, Gabriela
(author)
-
Dimas, Antigone S
(author)
-
Ingle, Catherine
(author)
-
Nestle, Frank O
(author)
-
di Meglio, Paola
(author)
-
Min, Josine L
(author)
-
Wilk, Alicja
(author)
-
Hammond, Christopher J
(author)
-
Hassanali, Neelam
(author)
-
Yang, Tsun-Po
(author)
-
Montgomery, Stephen B
(author)
-
O'Rahilly, Steve
(author)
-
Lindgren, Cecilia M
(author)
-
Zondervan, Krina T
(author)
-
Soranzo, Nicole
(author)
-
Barroso, Inês
(author)
-
Durbin, Richard
(author)
-
Ahmadi, Kourosh
(author)
-
Deloukas, Panos
(author)
-
McCarthy, Mark I
(author)
-
Dermitzakis, Emmanouil T
(author)
-
Spector, Timothy D
(author)
Related titles
-
In:PLOS Genetics: Public Library of Science (PLoS)7:21553-73901553-7404
Internet link
Find in a library
To the university's database
- By the author/editor
-
Nica, Alexandra ...
-
Parts, Leopold
-
Glass, Daniel
-
Nisbet, James
-
Barrett, Amy
-
Sekowska, Magdal ...
-
show more...
-
Travers, Mary
-
Potter, Simon
-
Grundberg, Elin
-
Small, Kerrin
-
Hedman, Asa K
-
Bataille, Veroni ...
-
Tzenova Bell, Jo ...
-
Surdulescu, Gabr ...
-
Dimas, Antigone ...
-
Ingle, Catherine
-
Nestle, Frank O
-
di Meglio, Paola
-
Min, Josine L
-
Wilk, Alicja
-
Hammond, Christo ...
-
Hassanali, Neela ...
-
Yang, Tsun-Po
-
Montgomery, Step ...
-
O'Rahilly, Steve
-
Lindgren, Cecili ...
-
Zondervan, Krina ...
-
Soranzo, Nicole
-
Barroso, Inês
-
Durbin, Richard
-
Ahmadi, Kourosh
-
Deloukas, Panos
-
McCarthy, Mark I
-
Dermitzakis, Emm ...
-
Spector, Timothy ...
-
show less...
- About the subject
-
- NATURAL SCIENCES
-
NATURAL SCIENCES
-
and Biological Scien ...
- Articles in the publication
-
PLOS Genetics
- By the university
-
Uppsala University