1. Association of vitamin D with risk of type 2 diabetes:A Mendelian randomisation study in European and Chinese adults
- Author
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Lu, Ling, Bennett, Derrick A., Millwood, Iona Y., Parish, Sarah, McCarthy, Mark I., Mahajan, Anubha, Lin, Xu, Bragg, Fiona, Guo, Yu, Holmes, Michael V., Afzal, Shoaib, Nordestgaard, Børge G., Bian, Zheng, Hill, Michael, Walters, Robin G., Li, Liming, Chen, Zhengming, and Clarke, Robert
- Subjects
Male ,Vitamin D/analogs & derivatives ,Physiology ,Organic chemistry ,Biochemistry ,Geographical Locations ,Endocrinology ,Mathematical and Statistical Techniques ,Risk Factors ,Medicine and Health Sciences ,Vitamin D ,China/epidemiology ,Latitude ,Geography ,Catabolism ,Vitamins ,Middle Aged ,Polymorphism, Single Nucleotide/genetics ,Body Fluids ,Physical sciences ,Europe ,Chemistry ,Blood ,Adipose Tissue ,Medicine ,Female ,Anatomy ,Statistics (Mathematics) ,Research Article ,Cartography ,Adult ,China ,Genotype ,Endocrine Disorders ,Research and Analysis Methods ,Diabetes Mellitus, Type 2/etiology ,Polymorphism, Single Nucleotide ,Blood Plasma ,Europe/epidemiology ,Chemical compounds ,Organic compounds ,Diabetes Mellitus ,Humans ,Statistical Methods ,Aged ,Biology and Life Sciences ,Mendelian Randomization Analysis ,Metabolism ,Biological Tissue ,Logistic Models ,Diabetes Mellitus, Type 2 ,Metabolic Disorders ,People and Places ,Earth Sciences ,Linear Models ,Mathematics ,Meta-Analysis - Abstract
Background Observational studies have reported that higher plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with lower risks of diabetes, but it is unclear if these associations are causal. The aim of this study was to test the relevance of 25(OH)D for type 2 diabetes using genetically instrumented differences in plasma 25(OH)D concentrations. Methods and findings Data were available on four 25(OH)D single nucleotide polymorphisms (SNPs; n = 82,464), plasma 25(OH)D concentrations (n = 13,565), and cases with diabetes (n = 5,565) in the China Kadoorie Biobank (CKB). The effects on risk of diabetes were assessed by a genetic score using two 25(OH)D synthesis SNPs (DHCR7-rs12785878 and CYP2R1-rs10741657), with and without the addition of SNPs affecting the transport (GC/DBP-rs2282679) and catabolism (CYP24A1-rs6013897) of 25(OH)D. The CKB results were combined in a meta-analysis of 10 studies for the 2 synthesis SNPs (n = 58,312 cases) and 7 studies for all 4 SNPs (n = 32,796 cases). Mean (SD) 25(OH)D concentration was 62 (20) nmol/l in CKB, and the per allele effects of genetic scores on 25(OH)D were 2.87 (SE 0.39) for the synthesis SNPs and 3.54 (SE 0.32) for all SNPs. A 25-nmol/l higher biochemically measured 25(OH)D was associated with a 9% (95% CI: 0%–18%) lower risk of diabetes in CKB. In a meta-analysis of all studies, a 25-nmol/l higher genetically instrumented 25(OH)D concentration was associated with a 14% (95% CI: 3%–23%) lower risk of diabetes (p = 0.01) using the 2 synthesis SNPs. An equivalent difference in 25(OH)D using a genetic score with 4 SNPs was not significantly associated with diabetes (odds ratio 8%, 95% CI: −1% to 16%, lower risk, p = 0.07), but had some evidence of pleiotropy. A limitation of the meta-analysis was the access only to study level rather than individual level data. Conclusions The concordant risks of diabetes for biochemically measured and genetically instrumented differences in 25(OH)D using synthesis SNPs provide evidence for a causal effect of higher 25(OH)D for prevention of diabetes., Robert Clarke and colleagues, using a Mendelian Randomisation approach, reveal a link between higher levels of vitamin D and type 2 diabetes prevention, based on data from 2 large cohorts., Author summary Why was this study done? There is a debate about whether low vitamin D status increases the risk of diabetes or is just a marker of overall poor health. Observational studies have demonstrated that individuals with higher vitamin D status in European populations have lower risks of developing type 2 diabetes. What did the researchers do and find? The present report, involving approximately 82,500 adults living in China, replicated the association of higher vitamin D status with lower risk of type 2 diabetes in Chinese adults. A combined analysis of over 58,000 cases and 370,000 controls in European and Chinese adults demonstrated that genetically instrumented increases in a circulating marker of vitamin D status, corresponding to increases achievable by vitamin D supplements, were associated with a 14% lower risk of diabetes. What do these findings mean? The concordant results of both the observational studies and the genetic studies indicate that higher vitamin D status is associated with lower risk of diabetes and provide support for a causally protective effect of higher vitamin D status for prevention of type 2 diabetes.
- Published
- 2018