uu.seUppsala universitets publikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
The architecture of gene regulatory variation across multiple human tissues: the MuTHER study.
Visa övriga samt affilieringar
2011 (Engelska)Ingår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 7, nr 2Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
2011. Vol. 7, nr 2
Nationell ämneskategori
Medicin och hälsovetenskap Biologiska vetenskaper
Identifikatorer
URN: urn:nbn:se:uu:diva-275702DOI: 10.1371/journal.pgen.1002003PubMedID: 21304890OAI: oai:DiVA.org:uu-275702DiVA: diva2:900699
Tillgänglig från: 2016-02-04 Skapad: 2016-02-04 Senast uppdaterad: 2017-11-30

Open Access i DiVA

Fulltext saknas

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Hedman, Asa K

Sök vidare i DiVA

Av författaren/redaktören
Hedman, Asa K
I samma tidskrift
PLoS Genetics
Medicin och hälsovetenskapBiologiska vetenskaper

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 195 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf