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.
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.
Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.|Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine, Kawasaki, Japan.
Ren
R
Matsuba
Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Minako
M
Imamura
Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine, Kawasaki, Japan.
Yasushi
Y
Tanaka
First Department of Internal Medicine, University of Toyama, Toyama, Japan.|Health Administration Center, University of Toyama, Toyama, Japan.
Minoru
M
Iwata
Health Center, Keio University School of Medicine, Tokyo, Japan.
Hiroshi
H
Hirose
Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan.
Kohei
K
Kaku
Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
Hiroshi
H
Maegawa
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.|Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Hirotaka
H
Watada
First Department of Internal Medicine, University of Toyama, Toyama, Japan.
Kazuyuki
K
Tobe
Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
Atsunori
A
Kashiwagi
Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Ryuzo
R
Kawamori
Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.|Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.|Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital, Nishihara, Japan.
Shiro
S
Maeda
D000368:Aged; D044466:Asian People / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human