Implication of Genetic Variants Near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in Type 2 Diabetes and Obesity in 6,719 Asians
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OBJECTIVE: Recent genome-wide association studies have identified six novel genes for type 2 diabetes and obesity and confirmed TCF7L2 as the major type 2 diabetes gene to date in Europeans. However, the implications of these genes in Asians are unclear. RESEARCH DESIGN AND METHODS: We studied 13 associated single nucleotide polymorphisms from these genes in 3,041 patients with type 2 diabetes and 3,678 control subjects of Asian ancestry from Hong Kong and Korea. RESULTS: We confirmed the associations of TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/CDKN2B, IGF2BP2, and FTO with risk for type 2 diabetes, with odds ratios ranging from 1.13 to 1.35 (1.3 x 10(-12) < P(unadjusted) < 0.016). In addition, the A allele of rs8050136 at FTO was associated with increased BMI in the control subjects (P(unadjusted) = 0.008). However, we did not observe significant association of any genetic variants with surrogate measures of insulin secretion or insulin sensitivity indexes in a subset of 2,662 control subjects. Compared with subjects carrying zero, one, or two risk alleles, each additional risk allele was associated with 17% increased risk, and there was an up to 3.3-fold increased risk for type 2 diabetes in those carrying eight or more risk alleles. Despite most of the effect sizes being similar between Asians and Europeans in the meta-analyses, the ethnic differences in risk allele frequencies in most of these genes lead to variable attributable risks in these two populations. CONCLUSIONS: Our findings support the important but differential contribution of these genetic variants to type 2 diabetes and obesity in Asians compared with Europeans.
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Despite heterogeneity across populations in risk allele frequency or effect size in type 2 diabetes genes, the combined effects of multiple genetic variants using genetic scores based on the number of risk alleles appear to be similar across different ethnic groups.
“Despite heterogeneity across populations in risk allele frequency or effect size in type 2 diabetes genes, the combined effects of multiple genetic variants using genetic scores based on the number of risk alleles appear to be similar across different ethnic groups.”
From Globalization of Diabetes (2011) · cites this paper as [41]
Typically, each risk allele increment is associated with a 10-20% increased risk of type 2 diabetes.
“Typically, each risk allele increment is associated with a 10–20% increased risk of type 2 diabetes (41,42).”
From Globalization of Diabetes (2011) · cites this paper as [41]
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- Authors
- Ng, M. C. Y., Park, K. S., Oh, B., Tam, C. H. T., Cho, Y. M., Shin, H. D., Lam, V. K. L., Ma, R. C. W., So, W. Y., Cho, Y. S., Kim, H.-L., Lee, H. K., Chan, J. C. N., & Cho, N. H.
- Affiliations
- Chinese University of Hong Kong (HK)
- Seoul National University (KR)
- Korea National Institute of Health (KR)
- Sogang University (KR)
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China
- Ajou University (KR)
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2008-08-01
- Volume
- 57
- Issue
- 8
- Pages
- 2226-2233
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2494677
- OpenAlex
- W2133972493
- Cited by
- 362
- References
- 37
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 9 · 2021: 7 · 2020: 9 · 2019: 9 · 2018: 12 · 2017: 14 · 2016: 12 · 2015: 25 · 2014: 38 · 2013: 26 · 2012: 31
- FWCI
- 27.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Ajou University
- Chinese University of Hong Kong
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- type 2 diabetes, obesity, genetic susceptibility, single nucleotide polymorphisms, TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/CDKN2B, IGF2BP2, FTO, rs8050136, body mass index, insulin secretion, insulin sensitivity, Asian populations, ethnic differences in genetic risk, risk allele frequency, attributable risk
- MeSH terms
- Zinc Transporter 8, Adult, Aged, Alleles, Diabetes Mellitus, Type 2, Female, Gene Frequency, Genotype, Hong Kong, Humans, Korea, Male, Middle Aged, Obesity, tRNA Methyltransferases, Transcription Factors, RNA-Binding Proteins, Homeodomain Proteins, Cyclin-Dependent Kinase Inhibitor p16, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Cation Transport Proteins, Asian People, Cyclin-Dependent Kinase Inhibitor p15, Cyclin-Dependent Kinase 5, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein
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