Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus
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Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. / Yasuda, Kazuki; Miyake, Kazuaki; Horikawa, Yukio; Hara, Kazuo; Osawa, Haruhiko; Furuta, Hiroto; Hirota, Yushi; Mori, Hiroyuki; Jonsson, Anna Elisabet; Sato, Yoshifumi; Yamagata, Kazuya; Hinokio, Yoshinori; Wang, He-Yao; Tanahashi, Toshihito; Nakamura, Naoto; Oka, Yoshitomo; Iwasaki, Naoko; Iwamoto, Yasuhiko; Yamada, Yuichiro; Seino, Yutaka; Maegawa, Hiroshi; Kashiwagi, Atsunori; Takeda, Jun; Maeda, Eiichi; Shin, Hyoung Doo; Cho, Young Min; Park, Kyong Soo; Lee, Hong Kyu; Ng, Maggie C Y; Ma, Ronald C W; So, Wing-Yee; Chan, Juliana C N; Lyssenko, Valeriya; Tuomi, Tiinamaija; Nilsson, Peter; Groop, Leif; Kamatani, Naoyuki; Sekine, Akihiro; Nakamura, Yusuke; Yamamoto, Ken; Yoshida, Teruhiko; Tokunaga, Katsushi; Itakura, Mitsuo; Makino, Hideichi; Nanjo, Kishio; Kadowaki, Takashi; Kasuga, Masato.
I: Nature Genetics, Bind 40, Nr. 9, 09.2008, s. 1092-7.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
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
VL - 40
SP - 1092
EP - 1097
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 9
ER -
ID: 46404685