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 x 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 x 10(-9); OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 x 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 x 10(-3); OR = 1.14, rs2237897, P = 2.4 x 10(-4); OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 x 10(-11); OR = 1.24, rs2237897, P = 1.2 x 10(-4); OR = 1.36).
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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 [700]
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- Authors
- Unoki, H., Takahashi, A., Kawaguchi, T., Hara, K., Horikoshi, M., Andersen, G., Ng, D. P. K., 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, E. S., Pedersen, O., Kamatani, N., Kadowaki, T., Kikkawa, R., Nakamura, Y., & Maeda, S.
- Affiliations
- RIKEN (JP)
- The University of Tokyo (JP)
- Novo Nordisk (Denmark) (DK)
- National University of Singapore (SG)
- University of Copenhagen (DK)
- Aarhus University (DK)
- Tokyo Women's Medical University (JP)
- Keio University (JP)
- Shiga University of Medical Science (JP)
- Kawasaki Medical School (JP)
- Juntendo University (JP)
- Singapore General Hospital (SG)
- Institute of Medical Science, The University of Tokyo (JP)
- Corresponding author
- Maeda, Shiro
- ORCID
- Takahashi, Atsushi
- Kawaguchi, Takahisa
- Hara, Kazuo
- Horikoshi, Momoko
- Andersen, Gitte
- Jørgensen, Torben
- Sandbæk, Annelli
- Lauritzen, Torsten
- Hansen, Torben
- Nurbaya, Siti
- Tsunoda, Tatsuhiko
- Kubo, Michiaki
- Babazono, Tetsuya
- Hirose, Hiroshi
- Hayashi, Matsuhiko
- Kashiwagi, Atsunori
- Kaku, Kohei
- Kawamori, Ryuzo
- Tai, E Shyong
- Pedersen, Oluf
- Kamatani, Naoyuki
- Kadowaki, Takashi
- Nakamura, Yusuke
- Maeda, Shiro
- Venue
- Nature Genetics
- Published
- 2008-08-17
- Volume
- 40
- Issue
- 9
- Pages
- 1098-1102
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2060270800
- Cited by
- 725
- References
- 6
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 20 · 2023: 18 · 2022: 17 · 2021: 25 · 2020: 32 · 2019: 27 · 2018: 31 · 2017: 23 · 2016: 49 · 2015: 53 · 2014: 57 · 2013: 56 · 2012: 66
- FWCI
- 37.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- National University of Singapore (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- KCNQ1, type 2 diabetes, single nucleotide polymorphisms, genetic susceptibility, voltage-gated potassium channels, linkage disequilibrium, East Asian populations, European populations, Japanese population, Singaporean population, Danish population
- MeSH terms
- Diabetes Mellitus, Type 2, Humans, Singapore, Gene Expression, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, White People, Asian People, KCNQ1 Potassium Channel, Genome-Wide Association Study
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