ArticleDiabetes2015
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.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Refining the Genetic Contribution to Type 2 Diabetes Subtypes.Diabetes, obesity & metabolism · 2026Article
- Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy.Metabolites · 2024Review
- Whole-genome sequencing study to identify candidate markers indicating susceptibility to type 2 diabetes in Bama miniature pigs.Animal models and experimental medicine · 2023Article
- Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules.Reproductive biology and endocrinology : RB&E · 2021Article
- Identification of Key Pathways and Genes in Obesity Using Bioinformatics Analysis and Molecular Docking Studies.Frontiers in endocrinology · 2021Article
- Bayesian shrinkage estimation of high dimensional causal mediation effects in omics studies.Biometrics · 2020Article
- The Māori and Pacific specific CREBRF variant and adult height.International journal of obesity (2005) · 2020Article
- Article
- Exploration of haplotype research consortium imputation for genome-wide association studies in 20,032 Generation Scotland participants.Genome medicine · 2017Article
- The Metabolic Syndrome in Men study: a resource for studies of metabolic and cardiovascular diseases.Journal of lipid research · 2017Article
- Article
- The Common p.R114W HNF4A Mutation Causes a Distinct Clinical Subtype of Monogenic Diabetes.Diabetes · 2016Article
- Type 2 diabetes: genetic data sharing to advance complex disease research.Nature reviews. Genetics · 2016Review
- Islet biology, the CDKN2A/B locus and type 2 diabetes risk.Diabetologia · 2016Review
- Genetics of Type 2 Diabetes: the Power of Isolated Populations.Current diabetes reports · 2016Review
- Glucose Induces Mouse β-Cell Proliferation via IRS2, MTOR, and Cyclin D2 but Not the Insulin Receptor.Diabetes · 2016Article
- A Robust Example of Collider Bias in a Genetic Association Study.American journal of human genetics · 2016Article
Corrections and comments
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Authors and funding
27 authors at 9 institutions in 5 countries.
Funding
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/m(2); 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.
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