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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 &lt;0.01). Among these SNPs, 16 have not been previously implicated as determinants of BMI or MetS. Cross-sectional data for obesity- and MetS-related phenotypes in 7,285 Japanese subjects were examined in a replication study. Among the 16 SNPs, three ( rs9491140 , rs145848316 , and rs7863248 ) were related to BMI in the replication cohort ( P &lt; 0.05). In conclusion, three SNPs [ rs9491140 of NKAIN2 (FDR = 0.003, P = 1.9 \u00d7 10<jats:sup>\u22125<\/jats:sup>), rs145848316 of KMT2C (FDR = 0.007, P = 4.5 \u00d7 10<jats:sup>\u22125<\/jats:sup>), and rs7863248 of AGTPBP1 (FDR = 0.006, P = 4.2 \u00d7 10<jats:sup>\u22125<\/jats:sup>)] were newly identified as susceptibility loci for BMI.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00117.2017","type":"journal-article","created":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T18:11:49Z","timestamp":1515780709000},"page":"179-189","source":"Crossref","is-referenced-by-count":10,"title":["Identification of three genetic variants as novel susceptibility loci for body mass index in a Japanese population"],"prefix":"10.1152","volume":"50","author":[{"given":"Yoshiki","family":"Yasukochi","sequence":"first","affiliation":[{"name":"Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu, Mie, Japan"},{"name":"CREST, Japan Science and Technology 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