Genetically determined vitamin D levels do not have a large effect on risk of type 1 diabetes in Europeans, according to a study published 25th February 2021 in the open-access journal PLOS Medicine by Despoina Manousaki from the CHU Sainte Justine and the University of Montreal, Canada and colleagues.
Type 1 diabetes is a relatively common autoimmune disease that inflicts substantial lifelong illness and significant economic burden. Its incidence is increasing worldwide, and there are no known interventions that can be used to prevent the disease. Vitamin D deficiency has been associated with type 1 diabetes in observational studies, but evidence of a causal effect from randomized controlled trials is lacking. In the new study, the researchers used a Mendelian randomization design to test whether genetically decreased vitamin D levels increase risk of type 1 diabetes. Mendelian randomization is a method of using measured variation in disease-related genes to examine the causal effect of an exposure on a disease. The two-sample Mendelian randomization study involved a vitamin D genome-wide association study (GWAS) including 443,734 Europeans, and a type 1 diabetes GWAS including 9,358 cases and 15,705 controls.
The results do not support a large effect of vitamin D levels on risk of type 1 diabetes (odds ratio: 1.09, 95% confidence interval: 0.86-1.40, p=0.48). However, smaller effects may exist, and the results may not be applicable to non-European populations. The findings suggest that the previous epidemiological associations between vitamin D and type 1 diabetes could be due to confounding factors, such as latitude and exposure to sunlight. According to Dr Manousaki: "Our findings do not support a large effect of vitamin D levels on type 1 diabetes, but there may be smaller effects which we could not detect. Until further evidence from large RCTs, we cannot suggest the use of vitamin D supplements as a strategy to prevent type 1 diabetes in individuals at risk, for instance siblings or offspring of people with type 1 diabetes".
Peer-reviewed; Experimental study; Humans
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Funding: DM is supported by JDRF (JDRF 3-PDF-2017-370-A-N). JBR is supported by the Canadian Institute of Health Research and Fonds de la recherche en santé du Quebec (FRSQ). A.H. is funded by the NMSS-ABF Clinician Scientist Development Award from the National Multiple Sclerosis Society (NMSS) and the Multiple Sclerosis Society of Canada (MSSC). NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol (BRC-1215-2001), the MRC Integrative Epidemiology Unit (MC_UU_00011) and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169).GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol MC_UU_00011/1. Funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests:JBR has worked as a consultant to GlaxoSmithKline and Deerfield Capital.GDS is a member of the Editorial Board of PLOS Medicine.
Citation: Manousaki D, Harroud A, Mitchell RE, Ross S, Forgetta V, Timpson NJ, et al. (2021) Vitamin D levels and risk of type 1 diabetes: A Mendelian randomization study. PLoS Med 18(2): e1003536. https://doi.org/10.1371/journal.pmed.1003536