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- Title
Genome-Wide Study of Subcutaneous and Visceral Adipose Tissue Reveals Novel Sex-Specific Adiposity Loci in Mexican Americans.
- Authors
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.; Chen, Yii-Der I
- Abstract
<bold>Objective: </bold>This study aimed to explore the genetic mechanisms of regional fat deposition, which is a strong risk factor for metabolic diseases beyond total adiposity.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
OBESITY complications; OBESITY genetics; ADIPOSE tissues; OBESITY &; society; HEALTH of Mexican Americans; OBESITY; HUMAN body composition; GENETIC polymorphisms; HISPANIC Americans; RESEARCH funding; PHENOTYPES; BODY mass index; SEQUENCE analysis; GENOTYPES
- Publication
Obesity (19307381), 2018, Vol 26, Issue 1, p202
- ISSN
1930-7381
- Publication type
journal article
- DOI
10.1002/oby.22074