4.8 Article

SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations

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NATURE GENETICS
卷 40, 期 9, 页码 1098-1102

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NATURE PUBLISHING GROUP
DOI: 10.1038/ng.208

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资金

  1. Ministry of Education, Culture, Sports, Science and Technology Japan
  2. Lundbeck Foundation Centre of Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LUCAMP)
  3. European Union [LSHM-CT-2004-512013]
  4. Danish Medical Research Council
  5. National Medical Research Council [NMRC/1115/2007]

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We conducted a genome-wide association study using 207,097 SNP markers in Japanese individuals with type 2 diabetes and unrelated controls, and identified KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) to be a strong candidate for conferring susceptibility to type 2 diabetes. We detected consistent association of a SNP in KCNQ1 (rs2283228) with the disease in several independent case-control studies (additive model P = 3.1 x 10(-12); OR = 1.26, 95% CI = 1.18-1.34). Several other SNPs in the same linkage disequilibrium (LD) block were strongly associated with type 2 diabetes (additive model: rs2237895, P = 7.3 x 10(-9); OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 x 10(-13); OR = 1.41, 95% CI = 1.29-1.55). The association of these SNPs with type 2 diabetes was replicated in samples from Singaporean (additive model: rs2237895, P = 8.5 x 10(-3); OR = 1.14, rs2237897, P = 2.4 x 10(-4); OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 x 10(-11); OR = 1.24, rs2237897, P = 1.2 x 10(-4); OR = 1.36).

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