Open AccessReplication 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
Author(s) -
Ren Matsuba,
Minako Imamura,
Yasushi Tanaka,
Minoru Iwata,
Hiroshi Hara,
Kohei Kaku,
Hiroshi Maegawa,
Hirotaka Watada,
Kazuyuki Tobe,
Atsunori Kashiwagi,
Ryuzo Kawamori,
Shiro Maeda
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0154093
Subject(s) - genome wide association study , single nucleotide polymorphism , odds ratio , type 2 diabetes , genetics , snp , meta analysis , genetic association , biology , population , locus (genetics) , genotype , medicine , diabetes mellitus , endocrinology , gene , environmental health
Aim 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. Methods 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. Results 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. Conclusions 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.