Back to Search
Start Over
Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion
- Source :
- Yaghootkar, H, Stancáková, A, Freathy, R M, Vangipurapu, J, Weedon, M N, Xie, W, Wood, A R, Ferrannini, E, Mari, A, Ring, S M, Lawlor, D A, Davey Smith, G, Jørgensen, T, Hansen, T, Pedersen, O, Steinthorsdottir, V, Guðbjartsson, D F, Thorleifsson, G, Thorsteinsdottir, U, Stefánsson, K, Hattersley, A T, Walker, M, Morris, A D, McCarthy, M I, Palmer, C N A, Laakso, M & Frayling, T M 2015, ' Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion ', Diabetes, vol. 64, no. 6, pp. 2279-2285 . https://doi.org/10.2337/db14-1456
- Publication Year :
- 2015
-
Abstract
- A recent study identified a low-frequency variant at CCND2 associated with lower risk of type 2 diabetes, enhanced insulin response to a glucose challenge, higher height, and, paradoxically, higher BMI. We aimed to replicate the strength and effect size of these associations in independent samples and to assess the underlying mechanism. We genotyped the variant in 29,956 individuals and tested its association with type 2 diabetes and related traits. The low-frequency allele was associated with a lower risk of type 2 diabetes (OR 0.53; P = 2 × 10−13; 6,647 case vs. 12,645 control subjects), higher disposition index (β = 0.07 log10; P = 2 × 10−11; n = 13,028), and higher Matsuda index of insulin sensitivity (β = 0.02 log10; P = 5 × 10−3; n = 13,118) but not fasting proinsulin (β = 0.01 log10; P = 0.5; n = 6,985). The low frequency allele was associated with higher adult height (β = 1.38 cm; P = 6 × 10−9; n = 13,927), but the association of the variant with BMI (β = 0.36 kg/m2; P = 0.02; n = 24,807), estimated in four population-based samples, was less than in the original publication where the effect estimate was biased by analyzing case subjects with type 2 diabetes and control subjects without diabetes separately. Our study establishes that a low-frequency allele in CCND2 halves the risk of type 2 diabetes primarily through enhanced insulin secretion.
- Subjects :
- medicine.medical_specialty
Genotype
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Type 2 diabetes
Lower risk
Article
Body Mass Index
Gene Frequency
Internal medicine
Insulin Secretion
Internal Medicine
medicine
Journal Article
Cyclin D2
Humans
Insulin
Allele
Allele frequency
Alleles
Genetic association
Proinsulin
business.industry
Research Support, Non-U.S. Gov't
medicine.disease
Endocrinology
Diabetes Mellitus, Type 2
business
Body mass index
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Yaghootkar, H, Stancáková, A, Freathy, R M, Vangipurapu, J, Weedon, M N, Xie, W, Wood, A R, Ferrannini, E, Mari, A, Ring, S M, Lawlor, D A, Davey Smith, G, Jørgensen, T, Hansen, T, Pedersen, O, Steinthorsdottir, V, Guðbjartsson, D F, Thorleifsson, G, Thorsteinsdottir, U, Stefánsson, K, Hattersley, A T, Walker, M, Morris, A D, McCarthy, M I, Palmer, C N A, Laakso, M & Frayling, T M 2015, ' Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion ', Diabetes, vol. 64, no. 6, pp. 2279-2285 . https://doi.org/10.2337/db14-1456
- Accession number :
- edsair.doi.dedup.....281028406d5ca033bd08424e0eea2fc0