期刊
DIABETES
卷 64, 期 6, 页码 2279-2285出版社
AMER DIABETES ASSOC
DOI: 10.2337/db14-1456
关键词
-
资金
- European Research Council [323195, SZ-50371]
- Wellcome Trust [085541/Z/08/Z, 072960/z/03/z, 099177/z12/z, 092731]
- Academy of Finland
- University of Eastern Finland
- Sigrid Juselius Foundation
- U.K. MRC
- University of Bristol
- Novo Nordisk Foundation Center for Basic Metabolic Research
- Novo Nordisk Foundation
- Lundbeck Foundation
- Danish Agency for Science, Technology and Innovation
- PhD School of Molecular Metabolism
- University of Southern Denmark
- Copenhagen Graduate School of Health and Medical Sciences
- Danish Research Council
- Danish Centre for Health Technology Assessment
- Research Foundation of Copenhagen County
- Ministry of Internal Affairs and Health
- Danish Heart Foundation
- Danish Pharmaceutical Association
- Augustinus Foundation
- Ib Henriksen Foundation
- Becket Foundation
- [SP/07 1008/24066]
- MRC [MC_UU_12013/1, MC_UU_12013/5, G0601261] Funding Source: UKRI
- Wellcome Trust [085541/Z/08/Z] Funding Source: Wellcome Trust
- Medical Research Council [MC_UU_12013/5, G0601261, MC_UU_12013/1, MC_PC_15018] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10219, NF-SI-0611-10099] Funding Source: researchfish
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 x 10(-13); 6,647 case vs. 12,645 control subjects), higher disposition index (beta = 0.07 log10; P = 2 x 10(-11); n = 13,028), and higher Matsuda index of insulin sensitivity (beta = 0.02 10g10; P = 5 x 10(-3); n = 13,118) but not fasting proinsulin (beta = 0.01 log10; P = 0.5; n = 6,985). The low frequency allele was associated with higher adult height (beta = 1.38 cm; P = 6 x 10(-9) n = 13,927), but the association of the variant with BMI (beta = 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据