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

• Published in: Nature genetics Vol. 40; no. 9; pp. 1092 - 1097
• Main Authors: Yasuda, Kazuki, Miyake, Kazuaki, Horikawa, Yukio, Hara, Kazuo, Osawa, Haruhiko, Furuta, Hiroto, Hirota, Yushi, Mori, Hiroyuki, Jonsson, Anna, 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2008; Nature Publishing Group
• Subjects: Agriculture; Alzheimer's disease; Animal Genetics and Genomics; Annan klinisk medicin; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chromosome Mapping; Clinical Medicine; Diabetes; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Disease susceptibility; Endocrine pancreas. Apud cells (diseases); Endocrinology and Diabetes; Endocrinopathies; Endokrinologi och diabetes; Etiopathogenesis. Screening. Investigations. Target tissue resistance; European Continental Ancestry Group; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic aspects; Genetic Predisposition to Disease; Genetic variation; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Genomics; Human Genetics; Humans; Insulin-Secreting Cells - physiology; KCNQ1 Potassium Channel - genetics; Klinisk medicin; letter; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Other Clinical Medicine; Polymorphism, Single Nucleotide; Risk factors; Science; Type 2 diabetes; Japan; Endocrinopathy; Type 2 diabetes; Variant; Metabolic diseases
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.207

Masato Kasuga and colleagues and Shiro Maeda and colleagues each report the independent identification of SNPs in KCNQ1 associated with type 2 diabetes in the Japanese population. Each group replicated the associations in other populations of East Asian and European descent. 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 P value (6.7 × 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 × 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 β-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.