| Literature DB >> 28257690 |
Mete Civelek1, Ying Wu2, Calvin Pan3, Chelsea K Raulerson2, Arthur Ko4, Aiqing He5, Charles Tilford5, Niyas K Saleem6, Alena Stančáková6, Laura J Scott7, Christian Fuchsberger7, Heather M Stringham7, Anne U Jackson7, Narisu Narisu8, Peter S Chines8, Kerrin S Small9, Johanna Kuusisto6, Brian W Parks3, Päivi Pajukanta4, Todd Kirchgessner5, Francis S Collins8, Peter S Gargalovic5, Michael Boehnke7, Markku Laakso6, Karen L Mohlke10, Aldons J Lusis11.
Abstract
Subcutaneous adipose tissue stores excess lipids and maintains energy balance. We performed expression quantitative trait locus (eQTL) analyses by using abdominal subcutaneous adipose tissue of 770 extensively phenotyped participants of the METSIM study. We identified cis-eQTLs for 12,400 genes at a 1% false-discovery rate. Among an approximately 680 known genome-wide association study (GWAS) loci for cardio-metabolic traits, we identified 140 coincident cis-eQTLs at 109 GWAS loci, including 93 eQTLs not previously described. At 49 of these 140 eQTLs, gene expression was nominally associated (p < 0.05) with levels of the GWAS trait. The size of our dataset enabled identification of five loci associated (p < 5 × 10-8) with at least five genes located >5 Mb away. These trans-eQTL signals confirmed and extended the previously reported KLF14-mediated network to 55 target genes, validated the CIITA regulation of class II MHC genes, and identified ZNF800 as a candidate master regulator. Finally, we observed similar expression-clinical trait correlations of genes associated with GWAS loci in both humans and a panel of genetically diverse mice. These results provide candidate genes for further investigation of their potential roles in adipose biology and in regulating cardio-metabolic traits.Entities:
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Year: 2017 PMID： 28257690 PMCID： PMC5339333 DOI： 10.1016/j.ajhg.2017.01.027
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025