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Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.
Civelek, Mete; Wu, Ying; Pan, Calvin; Raulerson, Chelsea K; Ko, Arthur; He, Aiqing; Tilford, Charles; Saleem, Niyas K; Stancáková, Alena; Scott, Laura J; Fuchsberger, Christian; Stringham, Heather M; Jackson, Anne U; Narisu, Narisu; Chines, Peter S; Small, Kerrin S; Kuusisto, Johanna; Parks, Brian W; Pajukanta, Päivi; Kirchgessner, Todd; Collins, Francis S; Gargalovic, Peter S; Boehnke, Michael; Laakso, Markku; Mohlke, Karen L; Lusis, Aldons J.
Afiliação
  • Civelek M; 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.
  • Wu Y; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Pan C; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Raulerson CK; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Ko A; 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.
  • He A; Bristol-Myers Squibb, Pennington, NJ 08534, USA.
  • Tilford C; Bristol-Myers Squibb, Pennington, NJ 08534, USA.
  • Saleem NK; Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio 70210, Finland.
  • Stancáková A; Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio 70210, Finland.
  • Scott LJ; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Fuchsberger C; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Stringham HM; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Jackson AU; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Narisu N; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chines PS; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Small KS; Department of Twin Research and Genetic Epidemiology, School of Medicine, King's College London, London SE1 7EH, UK.
  • Kuusisto J; Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio 70210, Finland.
  • Parks BW; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Pajukanta P; 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.
  • Kirchgessner T; Bristol-Myers Squibb, Pennington, NJ 08534, USA.
  • Collins FS; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Gargalovic PS; Bristol-Myers Squibb, Pennington, NJ 08534, USA.
  • Boehnke M; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Laakso M; Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio 70210, Finland.
  • Mohlke KL; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: mohlke@med.unc.edu.
  • Lusis AJ; 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 Mi
Am J Hum Genet ; 100(3): 428-443, 2017 Mar 02.
Article em En | MEDLINE | ID: mdl-28257690
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Cardiovasculares / Regulação da Expressão Gênica / Síndrome Metabólica / Locos de Características Quantitativas / Gordura Subcutânea Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Cardiovasculares / Regulação da Expressão Gênica / Síndrome Metabólica / Locos de Características Quantitativas / Gordura Subcutânea Idioma: En Ano de publicação: 2017 Tipo de documento: Article