Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits
Creators: name: Gargalovic, Peter S.
name: Jackson, Anne U.
name: Civelek, Mete
name: Tilford, Charles
name: Mohlke, Karen L.
name: Pan, Calvin
name: Kirchgessner, Todd
name: Ko, Arthur
name: Pajukanta, Päivi
name: Chines, Peter S.
name: He, Aiqing
name: Stringham, Heather M.
name: Collins, Francis S.
name: Wu, Ying
name: Fuchsberger, Christian
name: Boehnke, Michael
name: Small, Kerrin S.
name: Raulerson, Chelsea K.
name: Stančáková, Alena
name: Laakso, Markku
name: Parks, Brian W.
name: Saleem, Niyas K.
name: Scott, Laura J.
name: Narisu, Narisu
name: Lusis, Aldons J.
name: Kuusisto, Johanna
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2017

description: Accession Numbers Newly deposited human expression data can be obtained from the Gene Expression Omnibus with the accession number GEO: Download GSE70353. Supplemental Data Supplemental Data include 8 figures and 14 tables and can be found with this article online at http://dx.doi.org/10.1016/j.ajhg.2017.01.027. Supplemental Data Document S1. Figures S1–S8 and Tables S1–S14 Download Table S5. GWAS Summary Results Used in the Summary-Data-Based Mendelian-Randomization-Method Analysis Download Table S8. Adipose eQTLs Identified at GWAS Loci for Cardiometabolic Dieseases and Traits Download Table S9. Results of the Summary-Data-Based Mendelian-Randomization Analysis The source of the GWAS summary results are given in Table S5. Download Table S10. Results of the Causal-Inference Test The causal-inference test was performed for the GWAS index SNP, expression of the cis-eQTL gene, and inverse-normalized traits measured in the METSIM population. Download Table S11. Association of Gene Expression and Cardio-Metabolic Traits Download Table S14. Trans-eQTL Hotspots Identified in METSIM Adipose Tissue and Their Look ups in the MuTHER Cohort Red indicates a cis-regulated gene in the locus. Download Document S2. Article plus Supplemental Data Download Web Resources Efficient and Parallelizable Association Container Toolbox (EPACTS), http://genome.sph.umich.edu/wiki/EPACTS GWAS Catalog, https://www.ebi.ac.uk/gwas/ The Haplotype Reference Consortium, http://www.haplotype-reference-consortium.org METSIM and HMDP, https://systems.genetics.ucla.edu/ 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.