Beyond BMI: Genome-Wide Associations of Visceral Fat, Fat Mass, and Fat-Free Mass in Eastern Asian Populations.

Abstract

BMI is widely used to define obesity and may not capture heterogeneity in body fat distribution. Genetic studies of obesity have largely focused on BMI but not visceral fat and fat-free mass, which is particularly limited in East Asian populations. This study aimed to explore the genetic associations among body composition traits. We conducted genome-wide association studies (GWAS) of fat composition traits, including visceral fat, fat mass, and fat-free mass, in 14,121 adults from a population-based biobank. Bioelectrical impedance analysis was used for standardized body composition. GWAS were performed, followed by multinomial logistic regressions for associations across phenotype strata, adjusting for BMI and confounders. GWAS identified multiple SNPs significantly associated with visceral fat, fat mass, and fat-free mass. A variant within the TTN-rs794727539 was inversely associated with visceral fat and positively associated with fat-free mass, independent of BMI. Additional loci showed trait-specific associations, while many fat-mass-associated variants were attenuated after BMI adjustment, highlighting different genetic regulation of fat distribution. We found that visceral fat, fat mass, and fat-free mass were governed by partially distinct genetic mechanisms not fully captured by BMI. These results underscore the importance of incorporating fat composition phenotypes into genetic studies in East Asian populations.