TY - JOUR
T1 - Genome-Wide Haplotype Analysis of Cis Expression Quantitative Trait Loci in Monocytes
AU - Garnier, Sophie
AU - Truong, Vinh
AU - Brocheton, Jessy
AU - Zeller, Tanja
AU - Rovital, Maxime
AU - Wild, Philipp S.
AU - Ziegler, Andreas
AU - Munzel, Thomas
AU - Tiret, Laurence
AU - Blankenberg, Stefan
AU - Deloukas, Panos
AU - Erdmann, Jeannette
AU - Hengstenberg, Christian
AU - Samani, Nilesh J.
AU - Schunkert, Heribert
AU - Ouwehand, Willem H.
AU - Goodall, Alison H.
AU - Cambien, François
AU - Trégouët, David Alexandre
PY - 2013/1/1
Y1 - 2013/1/1
N2 - In order to assess whether gene expression variability could be influenced by several SNPs acting in cis, either through additive or more complex haplotype effects, a systematic genome-wide search for cis haplotype expression quantitative trait loci (eQTL) was conducted in a sample of 758 individuals, part of the Cardiogenics Transcriptomic Study, for which genome-wide monocyte expression and GWAS data were available. 19,805 RNA probes were assessed for cis haplotypic regulation through investigation of ~2,1×109 haplotypic combinations. 2,650 probes demonstrated haplotypic p-values >104-fold smaller than the best single SNP p-value. Replication of significant haplotype effects were tested for 412 probes for which SNPs (or proxies) that defined the detected haplotypes were available in the Gutenberg Health Study composed of 1,374 individuals. At the Bonferroni correction level of 1.2×10-4 (~0.05/412), 193 haplotypic signals replicated. 1000G imputation was then conducted, and 105 haplotypic signals still remained more informative than imputed SNPs. In-depth analysis of these 105 cis eQTL revealed that at 76 loci genetic associations were compatible with additive effects of several SNPs, while for the 29 remaining regions data could be compatible with a more complex haplotypic pattern. As 24 of the 105 cis eQTL have previously been reported to be disease-associated loci, this work highlights the need for conducting haplotype-based and 1000G imputed cis eQTL analysis before commencing functional studies at disease-associated loci.
AB - In order to assess whether gene expression variability could be influenced by several SNPs acting in cis, either through additive or more complex haplotype effects, a systematic genome-wide search for cis haplotype expression quantitative trait loci (eQTL) was conducted in a sample of 758 individuals, part of the Cardiogenics Transcriptomic Study, for which genome-wide monocyte expression and GWAS data were available. 19,805 RNA probes were assessed for cis haplotypic regulation through investigation of ~2,1×109 haplotypic combinations. 2,650 probes demonstrated haplotypic p-values >104-fold smaller than the best single SNP p-value. Replication of significant haplotype effects were tested for 412 probes for which SNPs (or proxies) that defined the detected haplotypes were available in the Gutenberg Health Study composed of 1,374 individuals. At the Bonferroni correction level of 1.2×10-4 (~0.05/412), 193 haplotypic signals replicated. 1000G imputation was then conducted, and 105 haplotypic signals still remained more informative than imputed SNPs. In-depth analysis of these 105 cis eQTL revealed that at 76 loci genetic associations were compatible with additive effects of several SNPs, while for the 29 remaining regions data could be compatible with a more complex haplotypic pattern. As 24 of the 105 cis eQTL have previously been reported to be disease-associated loci, this work highlights the need for conducting haplotype-based and 1000G imputed cis eQTL analysis before commencing functional studies at disease-associated loci.
UR - http://www.scopus.com/inward/record.url?scp=84873517235&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1003240
DO - 10.1371/journal.pgen.1003240
M3 - Journal articles
C2 - 23382694
AN - SCOPUS:84873517235
SN - 1553-7390
VL - 9
JO - PLoS Genetics
JF - PLoS Genetics
IS - 1
M1 - e1003240
ER -
