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SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations
Authors:Unoki Hiroyuki  Takahashi Atsushi  Kawaguchi Takahisa  Hara Kazuo  Horikoshi Momoko  Andersen Gitte  Ng Daniel P K  Holmkvist Johan  Borch-Johnsen Knut  Jørgensen Torben  Sandbaek Annelli  Lauritzen Torsten  Hansen Torben  Nurbaya Siti  Tsunoda Tatsuhiko  Kubo Michiaki  Babazono Tetsuya  Hirose Hiroshi  Hayashi Matsuhiko  Iwamoto Yasuhiko  Kashiwagi Atsunori  Kaku Kohei  Kawamori Ryuzo  Tai E Shyong  Pedersen Oluf  Kamatani Naoyuki  Kadowaki Takashi  Kikkawa Ryuichi  Nakamura Yusuke  Maeda Shiro
Affiliation:Laboratory for Endocrinology and Metabolism, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
Abstract: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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