Association of new loci identified in European genome-wide association studies with susceptibility to type 2 diabetes in the Japanese

• Published in: PloS one Vol. 6; no. 10; p. e26911
• Main Authors: Ohshige, Toshihiko, Iwata, Minoru, Omori, Shintaro, Tanaka, Yasushi, Hirose, Hiroshi, Kaku, Kohei, Maegawa, Hiroshi, Watada, Hirotaka, Kashiwagi, Atsunori, Kawamori, Ryuzo, Tobe, Kazuyuki, Kadowaki, Takashi, Nakamura, Yusuke, Maeda, Shiro
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26-10-2011; Public Library of Science (PLoS)
• Subjects: Analysis; Biology; Case-Control Studies; Chromosomal proteins; Chromosomes; Classification; Confidence intervals; Consortia; Deoxyribonucleic acid; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - ethnology; Diabetes Mellitus, Type 2 - genetics; Diabetes therapy; Disease susceptibility; DNA; Endocrinology; European Continental Ancestry Group - genetics; Fasting; Gene loci; Genetic aspects; Genetic Predisposition to Disease; Genetic testing; Genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Glucose; Glucose metabolism; Homeostasis; Humans; Insulin resistance; Internal medicine; Japan - epidemiology; KCNQ1 protein; Laboratories; Loci; Medical schools; Medicine; Mens health; Meta-analysis; Metabolism; Minority & ethnic groups; Physiological aspects; Polymorphism, Single Nucleotide; Potassium channels (voltage-gated); Regression analysis; Science; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Statistical analysis; Triglycerides; Type 2 diabetes; Womens health; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0026911

Several novel susceptibility loci for type 2 diabetes have been identified through genome-wide association studies (GWAS) for type 2 diabetes or quantitative traits related to glucose metabolism in European populations. To investigate the association of the 13 new European GWAS-derived susceptibility loci with type 2 diabetes in the Japanese population, we conducted a replication study using 3 independent Japanese case-control studies.
We examined the association of single nucleotide polymorphisms (SNPs) within 13 loci (MTNR1B, GCK, IRS1, PROX1, BCL11A, ZBED3, KLF14, TP53INP1, KCNQ1, CENTD2, HMGA2, ZFAND6 and PRC1) with type 2 diabetes using 4,964 participants (2,839 cases and 2,125 controls) from 3 independent Japanese samples. The association of each SNP with type 2 diabetes was analyzed by logistic regression analysis. Further, we performed combined meta-analyses for the 3 studies and previously performed Japanese GWAS data (4,470 cases vs. 3,071 controls). The meta-analysis revealed that rs2943641 in the IRS1 locus was significantly associated with type 2 diabetes, (P = 0.0034, OR = 1.15 95% confidence interval; 1.05-1.26) and 3 SNPs, rs10930963 in the MTNR1B locus, rs972283 in the KLF14 locus, and rs231362 in the KCNQ1 locus, had nominal association with type 2 diabetes in the present Japanese samples (P<0.05).
These results indicate that IRS1 locus may be common locus for type 2 diabetes across different ethnicities.