Genome-wide haplotype analysis of cis expression quantitative trait loci in monocytes..pdf (494.8 kB)
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Genome-wide haplotype analysis of cis expression quantitative trait loci in monocytes.

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posted on 14.07.2015, 11:08 by S. Garnier, V. Truong, J. Brocheton, T. Zeller, M. Rovital, P. S. Wild, A. Ziegler, Cardiogenics Consortium, T. Munzel, A. Tiret, S. Blankenberg, P. Deloukas, J. Erdmann, C. Hengstenberg, N. J. Samani, H. Schunkert, W. H. Ouwehand, A. H. Goodall, F. Cambien, D. A. Trégouët
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 × 10(9) haplotypic combinations. 2,650 probes demonstrated haplotypic p-values >10(4)-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. 1000 G 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 1000 G imputed cis eQTL analysis before commencing functional studies at disease-associated loci.

History

Citation

PLoS Genetics, 2013, 9 (1), e1003240

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cardiovascular Sciences

Version

VoR (Version of Record)

Published in

PLoS Genetics

Publisher

Public Library of Science

eissn

1553-7404

Acceptance date

27/11/2012

Copyright date

2013

Available date

14/07/2015

Publisher version

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003240

Language

en