Vitamin D and cause-specific vascular disease and mortality: a Mendelian randomisation study involving 99,012 Chinese and 106,911 European adults

Abstract

Background Randomised control trials and genetic analyses have demonstrated that vitamin D or 25-hydroxyvitamin D (25[OH]D) levels may not play a causal role in the development of cardiovascular disease. However, it is unclear if 25(OH)D is causally associated with cause-specific vascular disease and lipids. Therefore, we examined the causal association of 25(OH)D with myocardial infarction, stroke, ischaemic heart disease, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, and lipid levels among both Chinese and Europeans. Methods We used a Mendelian randomisation (MR) design in the China Kadoorie Biobank, the Copenhagen City Heart Study, and the Copenhagen General Population Study. The 25(OH)D-related genetic variants in the CYP2R1 and DCHR7 genes were genotyped in 99,012 Chinese adults and 106,911 Danish adults. Results In Chinese adults, plasma 25(OH)D levels were not significantly associated with cause-specific vascular disease or mortality, with the exception of intracerebral haemorrhage (HR, 1.09 [95% CI, 1.01,1.18] per 25 nmol/L higher plasma 25(OH)D). In Europeans, plasma 25(OH)D levels were inversely associated with all types of vascular diseases and mortality. However, MR analysis did not demonstrate causal associations of genetically increased 25(OH)D levels with cause-specific vascular diseases, or mortality in both Chinese and European adults. In addition, each 25 nmol/L higher 25(OH)D was observationally associated with lower total cholesterol and low-density lipoprotein cholesterol levels, but higher high-density lipoprotein cholesterol levels. Likewise, MR analysis showed that 25(OH)D levels were not causally associated with lipids in both Chinese and European adults after Bonferroni correction. Conclusions We found no evidence to support that genetically increased 25(OH)D was associated with a lower risk of ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and lipid levels in both Chinese and European adults. These results suggest that the inverse associations of vitamin D with vascular disease could be the result of confounding. Electronic supplementary material The online version of this article (10.1186/s12916-019-1401-y) contains supplementary material, which is available to authorized users.

Review of Recent Advances in Understanding the Role of Vitamin D in Reducing Cancer Risk: Breast, Colorectal, Prostate, and Overall Cancer

“…A recent article on the MR study stated (46) Another MR study published around the same time supported that statement. For the Copenhagen data sets, the HR for a 10-ng/ml increase in the MR genetically determined 25(OH)D concentration and cancer mortality rate was 0.97 (95% CI=0.94-1.10; p=0.06), whereas the HR for 10 ng/ml of serum 25(OH)D concentration was 0.93 (95% CI=0.88-0.98) (47). However, the HRs for 25(OH)D quartiles 1-4 were 1.00, 0.86 (95% CI=0.78-0.94), 0.87 (95% CI=0.78-0.96), and 0.79 (95% CI=0.71-0.89), respectively (p trend =9.7×10 -5 ).…”

Ablation of Vitamin D Signaling Compromises Cerebrovascular Adaptation to Carotid Artery Occlusion in Mice

“…Although Mendelian randomization analyses have failed to provide evidence for a causal association between vitamin D levels and cerebrovascular diseases [5][6][7], observational studies imply a strong link between vitamin D deficiency and risk [8][9][10][11], as well as severity, of ischemic stroke [12]. Ischemic stroke is one of the leading causes of death; up to 5% of stroke cases are due to occlusion of the carotid arteries [13,14].…”

Associations between outdoor temperature and bright sunlight with metabolites in two population-based European cohorts

“…However, animal models with adiposespecific overexpression or knockout of the VDR via the FABP4 promoter/enhancer element do not support a major role for vitamin D metabolism in mediating the associations between sunlight hours and the metabolome [34,35]. Furthermore, Mendelian Randomization studies have shown a lack of causal association between circulating vitamin D levels and T2D as well as lipid levels and causespecific vascular disease and mortality [36,37]. Similarly, genetic variation in the Vitamin D Receptor gene (VDR) has not been linked to either T2D or coronary artery disease risk [38,39].…”