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

China Kadoorie Biobank (CKB) collaborative group

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    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.

    Original languageEnglish
    Article number160
    Number of pages12
    JournalBMC Medicine
    Issue number1
    Publication statusPublished - 30 Aug 2019

    Bibliographical note

    © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
    International License (, which permits unrestricted use, distribution, and
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    This work was supported by the High-performance Computing Platform of Peking University and grants (2016YFC0900500, 2016YFC0900501, 2016YFC0900504) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/ 09/Z, 104085/Z/14/Z), National Natural Science Foundation of China (81390540, 81390544, 81390541), and Chinese Ministry of Science and Technology (2011BAI09B01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    Publisher Copyright:
    © 2019 The Author(s).


    • Cardiovascular diseases
    • Causal effect
    • Lipids
    • Mendelian randomisation
    • Vitamin D

    ASJC Scopus subject areas

    • Medicine(all)


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