A Genome-Wide Association Study on Abdominal Adiposity-Related Traits in Adult Korean Men

Abstract

<b><i>Introduction:</i></b> Although previous genome-wide association studies (GWASs) have identified genetic susceptibility loci for abdominal adiposity, GWASs on Asian samples remain scarce. Therefore, we performed a GWAS for abdominal adipose tissue depots in a Korean population. <b><i>Methods:</i></b> A total of 1,937 Korean men were included in the study. Areas of abdominal fat were quantified by computed tomography. We performed a GWAS analysis under an additive model, and a replication study was conducted on 480 additional Korean adult men. <b><i>Results:</i></b> In the discovery step, we identified a total of 10 single-nucleotide polymorphisms (SNPs) associated with adiposity indicators (<i>p</i> &#x3c; 1 × 10⁻⁵). The top SNP, rs1028014, for visceral adipose tissue (VAT) was located in the <i>ZMAT4</i> gene and remained significant after adjustment for body mass index (BMI). Three additional SNPs were also associated with VAT-adj-BMI and located within the <i>SLC26A10, FAM155A, and COL4A1-COL4A2</i> genes, respectively. In addition, we identified a SNP (rs4668224) of the <i>MYO3B</i> gene for visceral-to-subcutaneous fat ratio. For subcutaneous adipose tissue and total adipose tissue, two (rs6585735 and rs363527) and three SNPs (rs1487892, rs9357565, and rs1985358) were found, respectively. Overall, eight SNPs were used in the replication study; however, none of the SNPs reached our level of significance for replication (<i>p</i> &#x3c; 0.0063). Nevertheless, rs4773144 of <i>COL4A1-COL4A2</i> for VAT-adj-BMI was the most interesting SNP identified in previous GWASs for coronary artery disease (based on the same risk allele “G”), along with functional effects. <b><i>Conclusion:</i></b> This study suggests for the first time that an SNP (rs4773144) of <i>COL4A1-COL4A2</i> may contribute to the increase in VAT level, especially in adult Korean men.