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.
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Genetic evidence suggests that the KCNQ1 locus is associated with increased T2DM risk.
“Genetic evidence suggests that the KCNQ1 locus is associated with increased T2DM risk (700, 749).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [749]
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- Authors
- Yasuda, K., Miyake, K., Horikawa, Y., Hara, K., Osawa, H., Furuta, H., Hirota, Y., Mori, H., Jonsson, A., 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, H. D., Cho, Y. M., Park, K. S., Lee, H. K., Ng, M. C. Y., Ma, R. C. W., So, W.-Y., Chan, J. C. N., 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.
- Affiliations
- Kobe University (JP)
- Gifu University (JP)
- The University of Tokyo (JP)
- Ehime University (JP)
- Wakayama Medical University (JP)
- Lund University (SE)
- The University of Osaka (JP)
- Chinese Academy of Sciences (CN)
- Tohoku University (JP)
- Tokushima University (JP)
- Kyoto Prefectural University of Medicine (JP)
- Tokyo Women's Medical University (JP)
- Shiga University of Medical Science (JP)
- SNP Genetics (South Korea) (KR)
- Seoul National University (KR)
- Chinese University of Hong Kong (HK)
- Helsinki University Hospital (FI)
- RIKEN (JP)
- Kyushu University (JP)
- National Cancer Center Research Institute (JP)
- Corresponding author
- Kasuga, Masato
- ORCID
- Yasuda, Kazuki
- Horikawa, Yukio
- Hara, Kazuo
- Osawa, Haruhiko
- Furuta, Hiroto
- Hirota, Yushi
- Mori, Hiroyuki
- Jonsson, Anna
- Sato, Yoshifumi
- Yamagata, Kazuya
- Tanahashi, Toshihito
- Nakamura, Naoto
- Iwasaki, Naoko
- 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
- So, Wing-Yee
- Chan, Juliana C N
- Lyssenko, Valeriya
- Nilsson, Peter
- Groop, Leif
- Sekine, Akihiro
- Nakamura, Yusuke
- Yamamoto, Ken
- Tokunaga, Katsushi
- Makino, Hideichi
- Kadowaki, Takashi
- Kasuga, Masato
- Venue
- Nature Genetics
- Published
- 2008-08-17
- Volume
- 40
- Issue
- 9
- Pages
- 1092-1097
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1971751459
- Cited by
- 776
- References
- 8
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 20 · 2023: 20 · 2022: 16 · 2021: 31 · 2020: 24 · 2019: 27 · 2018: 27 · 2017: 39 · 2016: 51 · 2015: 54 · 2014: 53 · 2013: 53 · 2012: 85
- FWCI
- 41.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- KCNQ1, type 2 diabetes, genetic susceptibility, single nucleotide polymorphisms, insulin secretion, beta-cell function, HOMA-IR, Japanese population, East Asian populations
- MeSH terms
- Chromosome Mapping, Diabetes Mellitus, Type 2, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, White People, Asian People, Insulin-Secreting Cells, KCNQ1 Potassium Channel, Genome-Wide Association Study
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