Bone Mineral Density-Associated Polymorphisms Are Associated with Obesity-Related Traits in Korean Adults in a Sex-Dependent Manner
Obesity and osteoporosis share common physiological factors, including the presence of atherosclerosis, a risk factor for cardiometabolic disease, as well as a common progenitor that differentiates into both adipocytes and osteoblasts. Among the 23 polymorphisms associated with bone mineral density (BMD) in recent genome-wide association studies (GWASs), an Osterix polymorphism has been identified and associated with childhood obesity in girls. Therefore, we focused on elucidating polymorphisms associated with adulthood obesity in a sex-dependent manner among the previously published BMD-associated polymorphisms from GWASs. We performed 2 screenings of 18 BMD-associated polymorphisms for obesity-related traits in 2,362 adults aged >20 years. We excluded 13 polymorphisms showing deviations from Hardy–Weinberg equilibrium or no association with obesity-related traits (body mass index, waist circumference (WC), and waist-to-hip ratio). Among 5 selected polymorphisms (rs9594738 of RANKL, rs17066364 of NUFIP1, rs7227401 of OSBPL1A, and rs1856057 and rs2982573 of ESR1) analyzed, 2 polymorphisms (rs9594738 and rs17066364) were associated with obesity-related traits. We found sex-dependent associations such that the 4 polymorphisms (excluding rs9594738 of RANKL) were associated with abdominal traits such as WC and waist-to-hip ratio only in men. In addition, when the combined genetic risk score (GRS) for WC increase was calculated with 4 SNPs (rs9594738, rs17066364, rs7227401, and rs1856057) exhibiting similar trends for both sexes, the magnitude of the GRS effect for the WC increase was larger in men than in women (effect size = 0.856 cm, P = 0.0000452 for men; effect size = 0.598 cm, P = 0.00228 for women). In summary, we found 4 polymorphisms, previously related to osteoporosis, to be associated to obesity-related traits in a sex-dependent manner in Korean adults, particularly in men.