Identification of three genetic variants as novel susceptibility loci for body mass index in a Japanese population

Recent genome-wide association studies have identified various obesity or metabolic syndrome (MetS) susceptibility loci. However, most studies were conducted in a cross-sectional manner. To address this gap, we performed a longitudinal exome-wide association study to identify susceptibility loci for obesity and MetS in a Japanese population. We traced clinical data of 6,022 Japanese subjects who had annual health check-ups for several years (mean follow-up period, 5 yr) and genotyped ~244,000 genetic variants. The association of single nucleotide polymorphisms (SNPs) with body mass index (BMI) or the prevalence of obesity and MetS was examined in a generalized estimating equation model. Our longitudinal exome-wide association studies detected 21 BMI- and five MetS-associated SNPs (false discovery rate, FDR