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.
Published Web Location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740005/Abstract
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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