Abstract
We conducted a genome-wide association study of type 2 diabetes (T2D) using 459,359 SNPs in a Japanese population with a three-stage study design (stage 1, 4,470 cases and 3,071 controls; stage 2, 2,886 cases and 3,087 controls; stage 3, 3,622 cases and 2,356 controls). We identified new associations in UBE2E2 on chromosome 3 and in C2CD4A-C2CD4B on chromosome 15 at genome-wide significant levels (rs7612463 in UBE2E2, combined P = 2.27 × 10−9; rs7172432 in C2CD4A-C2CD4B, combined P = 3.66 × 10−9). The association of these two loci with T2D was replicated in other east Asian populations. In the European populations, the C2CD4A-C2CD4B locus was significantly associated with T2D, and a combined analysis of all populations gave P = 8.78 × 10−14, whereas the UBE2E2 locus did not show association to T2D. In conclusion, we identified two new loci at UBE2E2 and C2CD4A-C2CD4B associated with susceptibility to T2D.
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Acknowledgements
We thank all participating doctors and staff from collaborating institutes for providing DNA samples. We also thank the technical staff of the Laboratory for Endocrinology and Metabolism at the RIKEN Center for Genomic Medicine for providing technical assistance. We thank the technical staff of the Laboratory for Genotyping Development at the RIKEN Center for Genomic Medicine for SNP genotyping. We also thank all the participants and the staff of the BioBank Japan project. This work was partly supported by a grant from the Leading Project of Ministry of Education, Culture, Sports, Science and Technology Japan.
Funding for the Singapore portion of the study was supported by the National Medical Research Council (NMRC/1115/2007). We thank the staff of the National Healthcare Group Polyclinics and the National University of Singapore for their contributions towards the establishment of the Singapore Diabetes Cohort Study.
The Korean panel was supported by a grant from the Korea Health 21 Research and Development Project, Ministry of Health, Welfare, and Family Affairs, Republic of Korea (00-PJ3-PG6-GN07-001).
The Danish study was funded by grants from the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LuCAMP), European Union (EUGENE2) grant LSHM-CT-2004-512013, EXGENESIS (Health benefits of exercise: identification of genes and signaling pathways involved in effects of exercise on insulin resistance, obesity and the metabolic syndrome) grant LSHM-CT-2004- 005272 and the Danish Diabetes Association and the Danish Agency for Science, Technology and Innovation, grant no. 271-06-0539. The Inter99 was initiated by T. Jørgensen (primary investigator), K. Borch-Johnsen (co-primary investigator), H. Ibsen and T.F. Thomsen. The steering committee comprises T. Jørgensen, K. Borch-Johnsen and C. Pisinger. The ADDITION (The Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care) study Denmark was initiated by K. Borch-Johnsen (primary investigator), T. Lauritzen (primary investigator) and A. Sandbæk.
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T.K., S.M., T.Y. and K.H. planned and coordinated the study. Y.N. managed BioBank Japan. K.H., S.M., K.Y., M.H., T.Y., M.K., H.W., H.M., H.D.S., D.R.W., T.J., T.L., A.S., T.H., T.O., S.O., I.S., K.K., H.H., W.-Y.S., D.B., E.S.T., C.I., Y.T., A.K., R.K., M.K., O.P. and T.K. recruited and phenotyped or genotyped subject cohorts. A.T., T.T., N.K., S.M., K.H., M.N., H.F., M.O.-I., M.I., N.S., N.G., G.A., S.C., D.P.K.N., R.C.W.M., M.K., T.Y., K.K., J.C.N.C., K.S.P., P.F., T.H., O.P. and T.K. analyzed the genotyping data. T.Y., T.K., S.M. and K.H. wrote the manuscript. All authors contributed to the final version of the manuscript.
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Yamauchi, T., Hara, K., Maeda, S. et al. A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B. Nat Genet 42, 864–868 (2010). https://doi.org/10.1038/ng.660
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DOI: https://doi.org/10.1038/ng.660
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