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Genome-Wide Study of Subcutaneous and Visceral Adipose Tissue Reveals Novel Sex-Specific Adiposity Loci in Mexican Americans.

  • Author(s): Gao, Chuan;
  • Langefeld, Carl D;
  • Ziegler, Julie T;
  • Taylor, Kent D;
  • Norris, Jill M;
  • Chen, Yii-Der I;
  • Hellwege, Jacklyn N;
  • Guo, Xiuqing;
  • Allison, Matthew A;
  • Speliotes, Elizabeth K;
  • Rotter, Jerome I;
  • Bowden, Donald W;
  • Wagenknecht, Lynne E;
  • Palmer, Nicholette D
  • et al.

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OBJECTIVE:This study aimed to explore the genetic mechanisms of regional fat deposition, which is a strong risk factor for metabolic diseases beyond total adiposity. METHODS:A genome-wide association study of 7,757,139 single-nucleotide polymorphisms (SNPs) in 983 Mexican Americans (nmale  = 403; nfemale  = 580) from the Insulin Resistance Atherosclerosis Family Study was performed. Association analyses were performed with and without sex stratification for subcutaneous adipose tissue, visceral adipose tissue (VAT), and visceral-subcutaneous ratio (VSR) obtained from computed tomography. RESULTS:The strongest signal identified was SNP rs2185405 (minor allele frequencies [MAF] = 40%; PVAT  = 1.98 × 10-8 ) with VAT. It is an intronic variant of the GLIS family zinc finger 3 gene (GLIS3). In addition, SNP rs12657394 (MAF = 19%) was associated with VAT in males (Pmale  = 2.39×10-8 ; Pfemale  = 2.5 × 10-3 ). It is located intronically in the serum response factor binding protein 1 gene (SRFBP1). On average, male carriers of the variant had 24.6 cm2 increased VAT compared with noncarriers. Subsequently, genome-wide SNP-sex interaction analysis was performed. SNP rs10913233 (MAF = 14%; Pint  = 3.07 × 10-8 ) in PAPPA2 and rs10923724 (MAF = 38%; Pint  = 2.89 × 10-8 ) upstream of TBX15 were strongly associated with the interaction effect for VSR. CONCLUSIONS:Six loci were identified with genome-wide significant associations with fat deposition and interactive effects. These results provided genetic evidence for a differential basis of fat deposition between genders.

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