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 & 10 others Atsunori Kashiwagi, Kohei Kaku, Ryuzo Kawamori, E. Shyong Tai, Oluf Pedersen, Naoyuki Kamatani, Takashi Kadowaki, Ryuichi Kikkawa, Yusuke Nakamura, Shiro Maeda

Research output: Contribution to journalArticle

496 Citations (Scopus)

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 languageEnglish
Pages (from-to)1098-1102
Number of pages5
JournalNature Genetics
Volume40
Issue number9
DOIs
Publication statusPublished - 01-09-2008

Fingerprint

Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
Population
Voltage-Gated Potassium Channels
Genome-Wide Association Study
Linkage Disequilibrium
Case-Control Studies

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Unoki, H., Takahashi, A., Kawaguchi, T., Hara, K., Horikoshi, M., Andersen, G., ... 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
Unoki, Hiroyuki ; Takahashi, Atsushi ; Kawaguchi, Takahisa ; Hara, Kazuo ; Horikoshi, Momoko ; Andersen, Gitte ; Ng, Daniel P.K. ; Holmkvist, Johan ; Borch-Johnsen, Knut ; Jørgensen, Torben ; Sandbæk, 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. / SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. In: Nature Genetics. 2008 ; Vol. 40, No. 9. pp. 1098-1102.
@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",
year = "2008",
month = "9",
day = "1",
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

SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. / Unoki, Hiroyuki; Takahashi, Atsushi; Kawaguchi, Takahisa; Hara, Kazuo; Horikoshi, Momoko; Andersen, Gitte; Ng, Daniel P.K.; Holmkvist, Johan; Borch-Johnsen, Knut; Jørgensen, Torben; Sandbæk, 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.

In: Nature Genetics, Vol. 40, No. 9, 01.09.2008, p. 1098-1102.

Research output: Contribution to journalArticle

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

PY - 2008/9/1

Y1 - 2008/9/1

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).

UR - http://www.scopus.com/inward/record.url?scp=50449085212&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50449085212&partnerID=8YFLogxK

U2 - 10.1038/ng.208

DO - 10.1038/ng.208

M3 - Article

VL - 40

SP - 1098

EP - 1102

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 9

ER -

Unoki H, Takahashi A, Kawaguchi T, Hara K, Horikoshi M, Andersen G et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nature Genetics. 2008 Sep 1;40(9):1098-1102. https://doi.org/10.1038/ng.208