Garnier, Sophie and Vinh Truong, and Brocheton, Jessy and Zeller, Tanja and Rovital, Maxime and Wild, Philipp S. and Ziegler, Andreas and Munzel, Thomas and Tiret, Laurence and Blankenberg, Stefan and Deloukas, Panos and Erdmann, Jeannette and Hengstenberg, Christian and Samani, Nilesh J. and Schunkert, Heribert and Ouwehand, Willem H. and Goodall, Alison H. and Cambien, Francois and Tregouet, David-Alexandre (2013) Genome-Wide Haplotype Analysis of Cis Expression Quantitative Trait Loci in Monocytes. PLOS GENETICS, 9 (1): e1003240. ISSN 1553-7404,
Full text not available from this repository. (Request a copy)Abstract
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 similar to 2,1 x 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 x 10(-4) (similar to 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLOBAL GENE-EXPRESSION; MYOCARDIAL-INFARCTION; SUSCEPTIBILITY LOCI; ASSOCIATION; DISEASE; RISK; VARIANTS; POLYMORPHISMS; POPULATION; GENOTYPES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Apr 2020 08:05 |
| Last Modified: | 29 Apr 2020 08:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17482 |
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