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Min, J.L.* ; Taylor, J.M.* ; Richards, J.B.* ; Watts, T.* ; Pettersson, F.H.* ; Broxholme, J.* ; Ahmadi, K.R.* ; Surdulescu, G.L.* ; Lowy, E.* ; Gieger, C. ; Newton-Cheh, C.* ; Perola, M.* ; Soranzo, N.* ; Surakka, I.* ; Lindgren, C.M.* ; Ragoussis, J.* ; Morris, A.P.* ; Cardon, L.R.* ; Spector, T.D.* ; Zondervan, K.T.*

The use of genome-wide eQTL associations in lymphoblastoid cell lines to identify novel genetic pathways involved in complex traits.

PLoS ONE 6:e22070 (2011)
Verlagsversion Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The integrated analysis of genotypic and expression data for association with complex traits could identify novel genetic pathways involved in complex traits. We profiled 19,573 expression probes in Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs) from 299 twins and correlated these with 44 quantitative traits (QTs). For 939 expressed probes correlating with more than one QT, we investigated the presence of eQTL associations in three datasets of 57 CEU HapMap founders and 86 unrelated twins. Genome-wide association analysis of these probes with 2.2 m SNPs revealed 131 potential eQTLs (1,989 eQTL SNPs) overlapping between the HapMap datasets, five of which were in cis (58 eQTL SNPs). We then tested 535 SNPs tagging the eQTL SNPs, for association with the relevant QT in 2,905 twins. We identified nine potential SNP-QT associations (P<0.01) but none significantly replicated in five large consortia of 1,097-16,129 subjects. We also failed to replicate previous reported eQTL associations with body mass index, plasma low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides levels derived from lymphocytes, adipose and liver tissue. Our results and additional power calculations suggest that proponents may have been overoptimistic in the power of LCLs in eQTL approaches to elucidate regulatory genetic effects on complex traits using the small datasets generated to date. Nevertheless, larger tissue-specific expression data sets relevant to specific traits are becoming available, and should enable the adoption of similar integrated analyses in the near future.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter COMMON VARIANTS; MICROARRAY PLATFORMS; EXPRESSION ANALYSES; LOCI; DISEASE; RISK; METAANALYSIS; POPULATIONS; NUCLEOTIDE; PHENOTYPES
Sprache englisch
Veröffentlichungsjahr 2011
HGF-Berichtsjahr 2011
ISSN (print) / ISBN 1932-6203
Zeitschrift PLoS ONE
Quellenangaben Band: 6, Heft: 7, Seiten: , Artikelnummer: e22070 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Genetic Epidemiology (IGE)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504100-001
PubMed ID 21789213
DOI 10.1371/journal.pone.0022070
WOS ID 000292811700020
Scopus ID 79960332127
Erfassungsdatum 2011-09-19
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