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

Hiroyuki Unoki; Atsushi Takahashi; Takahisa Kawaguchi; Kazuo Hara; Momoko Horikoshi; Gitte Andersen; Daniel P.K. Ng; Johan Holmkvist; Knut Borch-Johnsen; Torben Jørgensen; Annelli Sandbæk; Torsten Lauritzen; Torben Hansen; Siti Nurbaya; Tatsuhiko Tsunoda; Michiaki Kubo; Tetsuya Babazono; Hiroshi Hirose; Matsuhiko Hayashi; Yasuhiko Iwamoto; Atsunori Kashiwagi; Kohei Kaku; Ryuzo Kawamori; E. Shyong Tai; Oluf Pedersen; Naoyuki Kamatani; Takashi Kadowaki; Ryuichi Kikkawa; Yusuke Nakamura; Shiro Maeda

doi:10.1038/ng.208

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

Hiroyuki Unoki, Atsushi Takahashi, Takahisa Kawaguchi, Kazuo Hara, Momoko Horikoshi, Gitte Andersen, Daniel P.K. Ng, Johan Holmkvist, Knut Borch-Johnsen, Torben Jørgensen, Annelli Sandbæk, Torsten Lauritzen, Torben Hansen, Siti Nurbaya, Tatsuhiko Tsunoda, Michiaki Kubo, Tetsuya Babazono, Hiroshi Hirose, Matsuhiko Hayashi, Yasuhiko IwamotoAtsunori Kashiwagi, Kohei Kaku, Ryuzo Kawamori, E. Shyong Tai, Oluf Pedersen, Naoyuki Kamatani, Takashi Kadowaki, Ryuichi Kikkawa, Yusuke Nakamura, Shiro Maeda

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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 × 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 × 10^-9; OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 × 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 × 10 ^-3; OR = 1.14, rs2237897, P = 2.4 × 10^-4; OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 × 10 ^-11; OR = 1.24, rs2237897, P = 1.2 × 10^-4; OR = 1.36).

Original language	English
Pages (from-to)	1098-1102
Number of pages	5
Journal	Nature Genetics
Volume	40
Issue number	9
DOIs	https://doi.org/10.1038/ng.208
Publication status	Published - 09-2008
Externally published	Yes

All Science Journal Classification (ASJC) codes

Genetics

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10.1038/ng.208

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Unoki, H., Takahashi, A., Kawaguchi, T., Hara, K., Horikoshi, M., Andersen, G., Ng, D. P. K., Holmkvist, J., Borch-Johnsen, K., Jørgensen, T., Sandbæk, A., Lauritzen, T., Hansen, T., Nurbaya, S., Tsunoda, T., Kubo, M., Babazono, T., Hirose, H., Hayashi, M., ... Maeda, S. (2008). SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nature Genetics, 40(9), 1098-1102. https://doi.org/10.1038/ng.208

@article{97f39a1468574541901e44fd8a24d563,

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

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 × 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 × 10-9; OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 × 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 × 10 -3; OR = 1.14, rs2237897, P = 2.4 × 10-4; OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 × 10 -11; OR = 1.24, rs2237897, P = 1.2 × 10-4; OR = 1.36).",

author = "Hiroyuki Unoki and Atsushi Takahashi and Takahisa Kawaguchi and Kazuo Hara and Momoko Horikoshi and Gitte Andersen and Ng, {Daniel P.K.} and Johan Holmkvist and Knut Borch-Johnsen and Torben J{\o}rgensen and Annelli Sandb{\ae}k and Torsten Lauritzen and Torben Hansen and Siti Nurbaya and Tatsuhiko Tsunoda and Michiaki Kubo and Tetsuya Babazono and Hiroshi Hirose and Matsuhiko Hayashi and Yasuhiko Iwamoto and Atsunori Kashiwagi and Kohei Kaku and Ryuzo Kawamori and Tai, {E. Shyong} and Oluf Pedersen and Naoyuki Kamatani and Takashi Kadowaki and Ryuichi Kikkawa and Yusuke Nakamura and Shiro Maeda",

note = "Funding Information: 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 Center for Genomic Medicine for providing technical assistance. This work was partly supported by a grant from the Leading Project of Ministry of Education, Culture, Sports, Science and Technology Japan. The Danish study was supported by Lundbeck Foundation Centre of Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LUCAMP), the European Union (EUGENE2, grant no. LSHM-CT-2004-512013) and the Danish Medical Research Council. Funding for Singapore arm of the study was supported by the National Medical Research Council (NMRC/1115/2007). We thank the staff of National Healthcare Group Polyclinics and National University of Singapore for their contributions towards the establishment of the Singapore Diabetes Cohort Study.",

year = "2008",

month = sep,

doi = "10.1038/ng.208",

language = "English",

volume = "40",

pages = "1098--1102",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

}

Unoki, H, Takahashi, A, Kawaguchi, T, Hara, K, Horikoshi, M, Andersen, G, Ng, DPK, Holmkvist, J, Borch-Johnsen, K, Jørgensen, T, Sandbæk, A, Lauritzen, T, Hansen, T, Nurbaya, S, Tsunoda, T, Kubo, M, Babazono, T, Hirose, H, Hayashi, M, Iwamoto, Y, Kashiwagi, A, Kaku, K, Kawamori, R, Tai, ES, Pedersen, O, Kamatani, N, Kadowaki, T, Kikkawa, R, Nakamura, Y & Maeda, S 2008, 'SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations', Nature Genetics, vol. 40, no. 9, pp. 1098-1102. https://doi.org/10.1038/ng.208

TY - JOUR

T1 - SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations

AU - Unoki, Hiroyuki

AU - Takahashi, Atsushi

AU - Kawaguchi, Takahisa

AU - Hara, Kazuo

AU - Horikoshi, Momoko

AU - Andersen, Gitte

AU - Ng, Daniel P.K.

AU - Holmkvist, Johan

AU - Borch-Johnsen, Knut

AU - Jørgensen, Torben

AU - Sandbæk, Annelli

AU - Lauritzen, Torsten

AU - Hansen, Torben

AU - Nurbaya, Siti

AU - Tsunoda, Tatsuhiko

AU - Kubo, Michiaki

AU - Babazono, Tetsuya

AU - Hirose, Hiroshi

AU - Hayashi, Matsuhiko

AU - Iwamoto, Yasuhiko

AU - Kashiwagi, Atsunori

AU - Kaku, Kohei

AU - Kawamori, Ryuzo

AU - Tai, E. Shyong

AU - Pedersen, Oluf

AU - Kamatani, Naoyuki

AU - Kadowaki, Takashi

AU - Kikkawa, Ryuichi

AU - Nakamura, Yusuke

AU - Maeda, Shiro

N1 - Funding Information: 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 Center for Genomic Medicine for providing technical assistance. This work was partly supported by a grant from the Leading Project of Ministry of Education, Culture, Sports, Science and Technology Japan. The Danish study was supported by Lundbeck Foundation Centre of Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LUCAMP), the European Union (EUGENE2, grant no. LSHM-CT-2004-512013) and the Danish Medical Research Council. Funding for Singapore arm of the study was supported by the National Medical Research Council (NMRC/1115/2007). We thank the staff of National Healthcare Group Polyclinics and National University of Singapore for their contributions towards the establishment of the Singapore Diabetes Cohort Study.

PY - 2008/9

Y1 - 2008/9

N2 - 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 × 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 × 10-9; OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 × 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 × 10 -3; OR = 1.14, rs2237897, P = 2.4 × 10-4; OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 × 10 -11; OR = 1.24, rs2237897, P = 1.2 × 10-4; OR = 1.36).

AB - 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 × 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 × 10-9; OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 × 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 × 10 -3; OR = 1.14, rs2237897, P = 2.4 × 10-4; OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 × 10 -11; OR = 1.24, rs2237897, P = 1.2 × 10-4; OR = 1.36).

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

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