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Am J Hum Genet. 2017 Mar 2;100(3):428-443. doi: 10.1016/j.ajhg.2017.01.027.

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

Author information

1
Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
2
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
3
Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
4
Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
5
Bristol-Myers Squibb, Pennington, NJ 08534, USA.
6
Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio 70210, Finland.
7
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
8
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
9
Department of Twin Research and Genetic Epidemiology, School of Medicine, King's College London, London SE1 7EH, UK.
10
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: mohlke@med.unc.edu.
11
Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: jlusis@mednet.ucla.edu.

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.

PMID:
28257690
PMCID:
PMC5339333
DOI:
10.1016/j.ajhg.2017.01.027
[Indexed for MEDLINE]
Free PMC Article

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