TY - JOUR
T1 - Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals
AU - Takeuchi, F.
AU - Yamamoto, K.
AU - Katsuya, T.
AU - Nabika, T.
AU - Sugiyama, T.
AU - Fujioka, A.
AU - Isono, M.
AU - Ohnaka, K.
AU - Fujisawa, T.
AU - Nakashima, E.
AU - Ikegami, H.
AU - Nakamura, J.
AU - Yamori, Y.
AU - Yamaguchi, S.
AU - Kobayashi, S.
AU - Ogihara, T.
AU - Takayanagi, R.
AU - Kato, N.
N1 - Funding Information:
Acknowledgements This work was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation Organization (NIBIO), the Manpei Suzuki Diabetes Foundation, a grant from National Center for Global Health and Medicine (NCGM) and by the Ministry of Education, Cultures, Sports, Science and Technology, all of Japan. We acknowledge the outstanding contributions of the employees of NCGM, who provided technical and infrastructural support for this work. Above all, we thank the patients and study participants who made this work possible and who gave it value. We thank all the people who continuously support the Hospital-based Cohort Study at NCGM, the Amagasaki Study and the Kyushu University Fukuoka Cohort Study in Japan. We also thank S. Kono, M. Ogasawara, C. Makibayashi and the many physicians of the Amagasaki Medical Association for their contribution in collecting DNA samples and accompanying clinical information. Part of the DNA samples from type 2 diabetes cases used for this research were provided from the Leading Project for Personalized Medicine at the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2011/6
Y1 - 2011/6
N2 - Aims/hypothesis: In populations of East Asian descent, we performed a replication study of loci previously identified in populations of European descent as being associated with obesity measures such as BMI and type 2 diabetes.Methods: We genotyped 14 single nucleotide polymorphisms (SNPs) from 13 candidate loci that had previously been identified by genome-wide association meta-analyses for obesity measures in Europeans. Genotyping was done in 18,264 participants from two general Japanese populations. For SNPs showing an obesity association in Japanese individuals, we further examined diabetes associations in up to 6,781 cases and 7,307 controls from a subset of theoriginal, as well as from additional populations.Results: Significant obesity associations (p<0.1 two-tailed, concordant direction with previous reports) were replicated for 11 SNPs from the following ten loci in Japanese participants: SEC16B, TMEM18, GNPDA2, BDNF, MTCH2, BCDIN3D-FAIM2, SH2B1-ATP2A1, FTO, MC4R and KCTD15. The strongest effect was observed at TMEM18 rs4854344 (p=7.1×10 -7 for BMI). Among the 11 SNPs showing significant obesity association, six were also associated with diabetes (OR 1.05-1.17; p=0.04-2.4×10 -7) after adjustment for BMI in the Japanese. When meta-analysed with data from the previous reports, the BMIadjusted diabetes association was found to be highly significant for the FTO locus in East Asians (OR 1.13; 95% CI 1.09-1.18; p=7.8×10 -10) with substantial interethnic heterogeneity (p=0.003). Conclusions/interpretation: We confirmed that ten candidate loci are associated with obesity measures in the general Japanese populations. Six (of ten) loci exert diabetogenic effects in the Japanese, although relatively modest in size, and independently of increased adiposity.
AB - Aims/hypothesis: In populations of East Asian descent, we performed a replication study of loci previously identified in populations of European descent as being associated with obesity measures such as BMI and type 2 diabetes.Methods: We genotyped 14 single nucleotide polymorphisms (SNPs) from 13 candidate loci that had previously been identified by genome-wide association meta-analyses for obesity measures in Europeans. Genotyping was done in 18,264 participants from two general Japanese populations. For SNPs showing an obesity association in Japanese individuals, we further examined diabetes associations in up to 6,781 cases and 7,307 controls from a subset of theoriginal, as well as from additional populations.Results: Significant obesity associations (p<0.1 two-tailed, concordant direction with previous reports) were replicated for 11 SNPs from the following ten loci in Japanese participants: SEC16B, TMEM18, GNPDA2, BDNF, MTCH2, BCDIN3D-FAIM2, SH2B1-ATP2A1, FTO, MC4R and KCTD15. The strongest effect was observed at TMEM18 rs4854344 (p=7.1×10 -7 for BMI). Among the 11 SNPs showing significant obesity association, six were also associated with diabetes (OR 1.05-1.17; p=0.04-2.4×10 -7) after adjustment for BMI in the Japanese. When meta-analysed with data from the previous reports, the BMIadjusted diabetes association was found to be highly significant for the FTO locus in East Asians (OR 1.13; 95% CI 1.09-1.18; p=7.8×10 -10) with substantial interethnic heterogeneity (p=0.003). Conclusions/interpretation: We confirmed that ten candidate loci are associated with obesity measures in the general Japanese populations. Six (of ten) loci exert diabetogenic effects in the Japanese, although relatively modest in size, and independently of increased adiposity.
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U2 - 10.1007/s00125-011-2086-8
DO - 10.1007/s00125-011-2086-8
M3 - Article
C2 - 21369819
AN - SCOPUS:80052540977
SN - 0012-186X
VL - 54
SP - 1350
EP - 1359
JO - Diabetologia
JF - Diabetologia
IS - 6
ER -
