Replication Study in a Japanese Population of Six Susceptibility Loci for Type 2 Diabetes Originally Identified by a Transethnic Meta-Analysis of Genome-Wide Association Studies

• Published in: PloS one Vol. 11; no. 4; p. e0154093
• Main Authors: Matsuba, Ren, Imamura, Minako, Tanaka, Yasushi, Iwata, Minoru, Hirose, Hiroshi, Kaku, Kohei, Maegawa, Hiroshi, Watada, Hirotaka, Tobe, Kazuyuki, Kashiwagi, Atsunori, Kawamori, Ryuzo, Maeda, Shiro
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.04.2016; Public Library of Science (PLoS)
• Subjects: Aged; Asian Continental Ancestry Group - genetics; Biology and Life Sciences; Body mass; Body mass index; Body size; Confidence intervals; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Disease susceptibility; Endocrinology; Female; Gene loci; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotype; Hispanic Americans; Humans; Insulin resistance; Internal medicine; Japan - epidemiology; Kidney diseases; Laboratories; Loci; Male; Medicine; Medicine and Health Sciences; Meta-analysis; Metabolism; Middle Aged; Minority & ethnic groups; Multiplexing; Oct-4 protein; Octamer Transcription Factor-3 - genetics; Pathogenesis; Physical Sciences; Physiological aspects; Polymerase chain reaction; Polymorphism, Single Nucleotide; Population; Population studies; Regression analysis; Replication; Research and Analysis Methods; Risk factors; Science; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Statistical analysis; Studies; Type 2 diabetes; University graduates; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0154093

We performed a replication study in a Japanese population to evaluate the association between type 2 diabetes and six susceptibility loci (TMEM154, SSR1, FAF1, POU5F1, ARL15, and MPHOSPH9) originally identified by a transethnic meta-analysis of genome-wide association studies (GWAS) in 2014. We genotyped 7,620 Japanese participants (5,817 type 2 diabetes patients and 1,803 controls) for each of the single nucleotide polymorphisms (SNPs) using a multiplex polymerase chain reaction invader assay. The association of each SNP locus with the disease was evaluated using logistic regression analysis. Of the six SNPs examined in this study, four (rs6813195 near TMEM154, rs17106184 in FAF1, rs3130501 in POU5F1 and rs4275659 near MPHOSPH9) had the same direction of effect as in the original reports, but two (rs9505118 in SSR1 and rs702634 in ARL15) had the opposite direction of effect. Among these loci, rs3130501 and rs4275659 were nominally associated with type 2 diabetes (rs3130501; p = 0.017, odds ratio [OR] = 1.113, 95% confidence interval [CI] 1.019-1.215, rs4275659; p = 0.012, OR = 1.127, 95% CI 1.026-1.238, adjusted for sex, age and body mass index), but we did not observe a significant association with type 2 diabetes for any of the six evaluated SNP loci in our Japanese population. Our results indicate that effects of the six SNP loci identified in the transethnic GWAS meta-analysis are not major among the Japanese, although SNPs in POU5F1 and MPHOSPH9 loci may have some effect on susceptibility to type 2 diabetes in this population.