Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus

Kazuki Yasuda; Kazuaki Miyake; Yukio Horikawa; Kazuo Hara; Haruhiko Osawa; Hiroto Furuta; Yushi Hirota; Hiroyuki Mori; Anna Elisabet Jonsson; Yoshifumi Sato; Kazuya Yamagata; Yoshinori Hinokio; He-Yao Wang; Toshihito Tanahashi; Naoto Nakamura; Yoshitomo Oka; Naoko Iwasaki; Yasuhiko Iwamoto; Yuichiro Yamada; Yutaka Seino; Hiroshi Maegawa; Atsunori Kashiwagi; Jun Takeda; Eiichi Maeda; Hyoung Doo Shin; Young Min Cho; Kyong Soo Park; Hong Kyu Lee; Maggie C Y Ng; Ronald C W Ma; Wing-Yee So; Juliana C N Chan; Valeriya Lyssenko; Tiinamaija Tuomi; Peter Nilsson; Leif Groop; Naoyuki Kamatani; Akihiro Sekine; Yusuke Nakamura; Ken Yamamoto; Teruhiko Yoshida; Katsushi Tokunaga; Mitsuo Itakura; Hideichi Makino; Kishio Nanjo; Takashi Kadowaki; Masato Kasuga

doi:10.1038/ng.207

Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus

Kazuki Yasuda, Kazuaki Miyake, Yukio Horikawa, Kazuo Hara, Haruhiko Osawa, Hiroto Furuta, Yushi Hirota, Hiroyuki Mori, Anna Elisabet Jonsson, Yoshifumi Sato, Kazuya Yamagata, Yoshinori Hinokio, He-Yao Wang, Toshihito Tanahashi, Naoto Nakamura, Yoshitomo Oka, Naoko Iwasaki, Yasuhiko Iwamoto, Yuichiro Yamada, Yutaka SeinoHiroshi Maegawa, Atsunori Kashiwagi, Jun Takeda, Eiichi Maeda, Hyoung Doo Shin, Young Min Cho, Kyong Soo Park, Hong Kyu Lee, Maggie C Y Ng, Ronald C W Ma, Wing-Yee So, Juliana C N Chan, Valeriya Lyssenko, Tiinamaija Tuomi, Peter Nilsson, Leif Groop, Naoyuki Kamatani, Akihiro Sekine, Yusuke Nakamura, Ken Yamamoto, Teruhiko Yoshida, Katsushi Tokunaga, Mitsuo Itakura, Hideichi Makino, Kishio Nanjo, Takashi Kadowaki, Masato Kasuga

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

657 Citationer (Scopus)

Abstract

We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	40
Udgave nummer	9
Sider (fra-til)	1092-7
Antal sider	6
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.207
Status	Udgivet - sep. 2008

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Citationsformater

Yasuda, K., Miyake, K., Horikawa, Y., Hara, K., Osawa, H., Furuta, H., Hirota, Y., Mori, H., Jonsson, A. E., Sato, Y., Yamagata, K., Hinokio, Y., Wang, H.-Y., Tanahashi, T., Nakamura, N., Oka, Y., Iwasaki, N., Iwamoto, Y., Yamada, Y., ... Kasuga, M. (2008). Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nature Genetics, 40(9), 1092-7. https://doi.org/10.1038/ng.207

Yasuda, K, Miyake, K, Horikawa, Y, Hara, K, Osawa, H, Furuta, H, Hirota, Y, Mori, H, Jonsson, AE, Sato, Y, Yamagata, K, Hinokio, Y, Wang, H-Y, Tanahashi, T, Nakamura, N, Oka, Y, Iwasaki, N, Iwamoto, Y, Yamada, Y, Seino, Y, Maegawa, H, Kashiwagi, A, Takeda, J, Maeda, E, Shin, HD, Cho, YM, Park, KS, Lee, HK, Ng, MCY, Ma, RCW, So, W-Y, Chan, JCN, Lyssenko, V, Tuomi, T, Nilsson, P, Groop, L, Kamatani, N, Sekine, A, Nakamura, Y, Yamamoto, K, Yoshida, T, Tokunaga, K, Itakura, M, Makino, H, Nanjo, K, Kadowaki, T & Kasuga, M 2008, 'Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus', Nature Genetics, bind 40, nr. 9, s. 1092-7. https://doi.org/10.1038/ng.207

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title = "Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus",

abstract = "We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.",

keywords = "Asian Continental Ancestry Group, Chromosome Mapping, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Insulin-Secreting Cells, KCNQ1 Potassium Channel, Polymorphism, Single Nucleotide",

author = "Kazuki Yasuda and Kazuaki Miyake and Yukio Horikawa and Kazuo Hara and Haruhiko Osawa and Hiroto Furuta and Yushi Hirota and Hiroyuki Mori and Jonsson, {Anna Elisabet} and Yoshifumi Sato and Kazuya Yamagata and Yoshinori Hinokio and He-Yao Wang and Toshihito Tanahashi and Naoto Nakamura and Yoshitomo Oka and Naoko Iwasaki and Yasuhiko Iwamoto and Yuichiro Yamada and Yutaka Seino and Hiroshi Maegawa and Atsunori Kashiwagi and Jun Takeda and Eiichi Maeda and Shin, {Hyoung Doo} and Cho, {Young Min} and Park, {Kyong Soo} and Lee, {Hong Kyu} and Ng, {Maggie C Y} and Ma, {Ronald C W} and Wing-Yee So and Chan, {Juliana C N} and Valeriya Lyssenko and Tiinamaija Tuomi and Peter Nilsson and Leif Groop and Naoyuki Kamatani and Akihiro Sekine and Yusuke Nakamura and Ken Yamamoto and Teruhiko Yoshida and Katsushi Tokunaga and Mitsuo Itakura and Hideichi Makino and Kishio Nanjo and Takashi Kadowaki and Masato Kasuga",

year = "2008",

month = sep,

doi = "10.1038/ng.207",

language = "English",

volume = "40",

pages = "1092--7",

journal = "Nature Genetics",

issn = "1061-4036",

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T1 - Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus

AU - Yasuda, Kazuki

AU - Miyake, Kazuaki

AU - Horikawa, Yukio

AU - Hara, Kazuo

AU - Osawa, Haruhiko

AU - Furuta, Hiroto

AU - Hirota, Yushi

AU - Mori, Hiroyuki

AU - Jonsson, Anna Elisabet

AU - Sato, Yoshifumi

AU - Yamagata, Kazuya

AU - Hinokio, Yoshinori

AU - Wang, He-Yao

AU - Tanahashi, Toshihito

AU - Nakamura, Naoto

AU - Oka, Yoshitomo

AU - Iwasaki, Naoko

AU - Iwamoto, Yasuhiko

AU - Yamada, Yuichiro

AU - Seino, Yutaka

AU - Maegawa, Hiroshi

AU - Kashiwagi, Atsunori

AU - Takeda, Jun

AU - Maeda, Eiichi

AU - Shin, Hyoung Doo

AU - Cho, Young Min

AU - Park, Kyong Soo

AU - Lee, Hong Kyu

AU - Ng, Maggie C Y

AU - Ma, Ronald C W

AU - So, Wing-Yee

AU - Chan, Juliana C N

AU - Lyssenko, Valeriya

AU - Tuomi, Tiinamaija

AU - Nilsson, Peter

AU - Groop, Leif

AU - Kamatani, Naoyuki

AU - Sekine, Akihiro

AU - Nakamura, Yusuke

AU - Yamamoto, Ken

AU - Yoshida, Teruhiko

AU - Tokunaga, Katsushi

AU - Itakura, Mitsuo

AU - Makino, Hideichi

AU - Nanjo, Kishio

AU - Kadowaki, Takashi

AU - Kasuga, Masato

PY - 2008/9

Y1 - 2008/9

N2 - We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.

AB - We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.

KW - Asian Continental Ancestry Group

KW - Chromosome Mapping

KW - Diabetes Mellitus, Type 2

KW - European Continental Ancestry Group

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Insulin-Secreting Cells

KW - KCNQ1 Potassium Channel

KW - Polymorphism, Single Nucleotide

U2 - 10.1038/ng.207

DO - 10.1038/ng.207

M3 - Journal article

C2 - 18711367

SN - 1061-4036

VL - 40

SP - 1092

EP - 1097

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -