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Genetically predicted circulating vitamin C in relation to cardiovascular disease.

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Mason, Amy M 
Larsson, Susanna C 


AIM: We conducted a two-sample Mendelian randomization (MR) study to assess the associations of genetically predicted circulating vitamin C levels with cardiovascular diseases (CVDs). METHODS AND RESULTS: Ten lead single-nucleotide polymorphisms associated with plasma vitamin C levels at the genome-wide significance level were used as instrumental variables. Summary-level data for 15 CVDs were obtained from corresponding genetic consortia, the UK Biobank study, and the FinnGen consortium. The inverse-variance-weighted method was the primary analysis method, supplemented by the weighted median and MR-Egger methods. Estimates for each CVD from different sources were combined. Genetically predicted vitamin C levels were not associated with any CVD after accounting for multiple testing. However, there were suggestive associations of higher genetically predicted vitamin C levels (per 1 standard deviation increase) with lower risk of cardioembolic stroke [odds ratio, 0.79; 95% confidence interval (CI), 0.64, 0.99; P = 0.038] and higher risk of atrial fibrillation (odds ratio, 1.09; 95% CI, 1.00, 1.18; P = 0.049) in the inverse-variance-weighted method and with lower risk of peripheral artery disease (odds ratio, 0.76, 95% CI, 0.62, 0.93; P = 0.009) in the weighted median method. CONCLUSION: We found limited evidence with MR techniques for an overall protective role of vitamin C in the primary prevention of CVD. The associations of vitamin C levels with cardioembolic stroke, atrial fibrillation, and peripheral artery disease need further study.



Cardiovascular disease, Mendelian randomization, Vitamin C, Ascorbic Acid, Cardiovascular Diseases, Humans, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Risk Factors, Vitamins

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Eur J Prev Cardiol

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Oxford University Press (OUP)
European Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (116074)
British Heart Foundation (None)
Wellcome Trust (204623/Z/16/Z)
British Heart Foundation (CH/12/2/29428)
British Heart Foundation (RG/18/13/33946)
Medical Research Council (MC_UU_00002/7)