Differential Genetic and Epigenetic Effects of the Gene on Body Shape Indices and Metabolic Traits.

The gene is a key metabolic transcriptional transregulator with monoallelic maternal expression. variants are only associated with adipose tissue gene expression, and promoter methylation is strongly associated with age. This study investigated whether age, sex, and obesity mediate the effects of variants and DNA methylation status on body shape indices and metabolic traits. In total, the data of 78,742 and 1636 participants from the Taiwan Biobank were included in the regional plot association analysis for variants and methylation, respectively. Regional plot association studies revealed that the rs4731702 variant and the nearby strong linkage disequilibrium polymorphisms were the lead variants for lipid profiles, blood pressure status, insulin resistance surrogate markers, and metabolic syndrome mainly in female participants and for body shape indices mainly in obese women. Significant age-dependent associations between promoter methylation levels and body shape indices, and metabolic traits were also noted predominantly in female participants. variants and hypermethylation status were associated with metabolically healthy and unhealthy phenotypes, respectively, in obese individuals, and only the variants demonstrated a significant association with both higher adiposity and lower cardiometabolic risk in the same allele, revealing uncoupled excessive adiposity from its cardiometabolic comorbidities, especially in obese women. Variations of are associated with body shape indices, metabolic traits, insulin resistance, and metabolically healthy status. Differential genetic and epigenetic effects of are age-, sex- and obesity-dependent. These results provided a personalized reference for the management of cardiometabolic diseases in precision medicine.