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

ObjectiveThis study aimed to explore the genetic mechanisms of regional fat deposition, which is a strong risk factor for metabolic diseases beyond total adiposity.MethodsA 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.ResultsThe 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.ConclusionsSix 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.