We aimed to identify obesity-related single-nucleotide polymorphism (SNP) loci in a Korean population and construct an obesity genetic risk score (GRS) to examine the association of the genetic predisposition to obesity with insulin resistance (IR). In total, 9675 subjects were included, and 7666 of these subjects were used for replication. A GRS was constructed using the SNP loci that overlapped in both cohort sets. The subjects showed a trend toward an increase in body mass index, waist circumference, systolic/diastolic blood pressure, homeostatic model assessment (HOMA)-IR, HOMA-B, and levels of insulin, triglyceride, and alanine aminotransferase across the tertiles of obesity GRS, while the adiponectin level showed a trend toward a decrease with increasing GRS. The associations between the obesity GRS and the measures of fasting insulin, HOMA-IR, and adiponectin were significant after adjusting for confounding factors. Moreover, a significant association between obesity GRS and HOMA-IR was observed in subjects with abdominal obesity. The present results indicate that a predisposition to obesity may affect IR in the Korean population and that abdominal fat may alter or modify the genetic effects. Furthermore, the set of obesity-related genotypes and abdominal fat may play interactive roles in determining the risk of IR.
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