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Serum Vitamin D Levels do not Affect Susceptibility to EBV Infection – A Mendelian Randomization Study

Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Introduction Epstein–Barr virus (EBV) infection and low serum 25-hydroxyvitamin D (25OHD) levels are strongly associated with multiple sclerosis (MS). We investigated whether genetically proxied serum vitamin D levels are causally linked to EBV infection, assessed by serology and detectable EBV DNA, using Mendelian randomisation (MR). Methods We conducted two-sample cis-MR using genetic instruments associated with serum 25OHD concentrations, restricted to variants near genes implicated in vitamin D metabolism. Outcomes included EBV seropositivity, antibody responses to four EBV antigens, detectable EBV DNA in blood and saliva, and MS case status as a positive control. Results Genetically proxied vitamin D levels had no clear effect on EBV seropositivity (odds ratio per standard deviation (SD) increase in rank-based inverse-normal transformation (RINT) 25OHD: 1.76, 95% confidence interval [CI] 0.83–3.73) or antibody responses to EBV antigens. No significant associations were observed with detectable EBV DNA in blood (beta 0.02, 95% CI −0.004 to 0.04) or saliva (beta 0.02, 95% CI −0.23 to 0.26). In contrast, genetically proxied vitamin D levels were associated with reduced MS risk (odds ratio per SD increase in RINT 25OHD 0.67, 95% CI 0.54–0.84). Discussion We found no clear evidence that genetically proxied vitamin D levels causally influence EBV serological responses or detectable EBV DNA in blood or saliva. The protective association with MS supports previous genetic evidence. These findings suggest that vitamin D and EBV may influence MS risk through distinct pathways, although effects specific to early-life vitamin D exposure remain possible.
Source: medRxiv
DOI: 10.64898/2026.10.29.26366817
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W7225005749
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