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Genetically Determined Vitamin D Levels Not Linked to T1DM

THURSDAY, March 11, 2021 -- Genetically determined vitamin D levels do not appear to have a large effect on the risk for type 1 diabetes in Europeans, according to research published online Feb. 25 in PLOS Medicine.

Despoina Manousaki, M.D., Ph.D., from the University of Montreal, and colleagues used Mendelian randomization (MR) to examine whether genetically reduced vitamin D levels are causally associated with type 1 diabetes. Single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25[OH]D) levels in a large vitamin D genome-wide association study on 443,734 Europeans were identified, and their corresponding effect estimates were examined on type 1 diabetes risk from a large meta-analysis of 12 studies.

The researchers identified 69 lead independent common SNPs as genome-wide significant for 25(OH)D; these explained 3.1 percent of the variation in 25(OH)D levels. A one-standard deviation decrease in standardized natural log-transformed 25(OH)D was not associated with an increased risk for type 1 diabetes in MR analyses. Using three pleiotropy robust MR methods and in sensitivity analyses excluding SNPs associated with serum lipid levels, body composition, blood traits, and type 2 diabetes, the results were similar.

"Our results identified no large impact of a genetically determined reduction in 25(OH)D levels on type 1 diabetes risk. This provides critical insight into a complex disease that remains poorly understood," the authors write. "Our findings imply that the observational associations between 25(OH)D and risk of type 1 diabetes might be due to environmental confounders."

One author disclosed financial ties to GlaxoSmithKline and Deerfield Capital.

Abstract/Full Text

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