Vitamin D levels, assessment of evidence for an association between vitamin D deficiency and atherosclerosis: a two-way Mendelian randomization study

Background and Aim

Previous studies have shown an association between vitamin D and atherosclerosis, but whether there is a causal relationship between the two is not yet clear and requires further study.The analytical approach of a two-sample Mendelian randomization study was used to further investigate the effect of vitamin D on AS.

Methods and Results

Vitamin D levels, vitamin D deficiency, and AS (including coronary atherosclerosis, cerebral atherosclerosis, aortic atherosclerosis, and peripheral atherosclerosis) were analyzed in samples from the Gwas database, all of which were of European origin. To assess the presence of reverse causality, data from the vitamin D-related samples were analyzed by reverse MR as an outcome.

Forward MR analyses of vitamin D levels, vitamin D deficiency, and atherosclerosis were negative, i.e., there was no positive causal association. For sensitivity analysis, Cochran’s Q test suggested no heterogeneity, and MR-Egger showed no evidence of horizontal pleiotropy. In contrast, our subsequent inverse MR analysis showed a causal association between peripheral atherosclerosis and vitamin D deficiency, i.e., peripheral atherosclerosis can cause the development of vitamin D deficiency. Sensitivity analyses did not reveal the presence of heterogeneity and horizontal pleiotropy. Leave-one-out analysis showed good robustness of the corresponding SNPs without bias. MR analyses between the other three types of atherosclerosis and vitamin D levels, and vitamin D deficiency, resulted in no causal association.

Conclusions

Our MR analysis identified peripheral atherosclerosis as a factor in the pathogenesis of vitamin D deficiency, which provides a reference for subsequent research and treatment of this disease.

Lay summary

We found through MR means that there is no positive causality between vitamin D and atherosclerosis, and it is unexpected that it is found that the outer peripheral atherosclerosis can cause vitamin D deficiency.