Dataset Information

Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.

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.

SUBMITTER: Civelek M

PROVIDER: S-EPMC5339333 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.

Civelek Mete M Wu Ying Y Pan Calvin C Raulerson Chelsea K CK Ko Arthur A He Aiqing A Tilford Charles C Saleem Niyas K NK Stančáková Alena A Scott Laura J LJ Fuchsberger Christian C Stringham Heather M HM Jackson Anne U AU Narisu Narisu N Chines Peter S PS Small Kerrin S KS Kuusisto Johanna J Parks Brian W BW Pajukanta Päivi P Kirchgessner Todd T Collins Francis S FS Gargalovic Peter S PS Boehnke Michael M Laakso Markku M Mohlke Karen L KL Lusis Aldons J AJ

American journal of human genetics 20170301 3

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 ...[more]

PMID: 28257690

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Dataset Information

Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.

Publications

Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.

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