Objective: To investigate the causal relationship between the risk of multiple sclerosis (MS) and modifiable lifestyle factors using two-sample Mendelian randomization analysis.
Methods: The study assessed exposures and outcomes using genome-wide significant single nucleotide polymorphisms (SNPs) found in earlier studies from different consortia. This study evaluated a number of exposures, including vitamin D levels, age at smoking initiation, smoking intensity, cheese, salad, processed meat and coffee intake, BMI, and lipid biomarkers. MS is the outcome of this paper. The genetic data for MS were obtained from UK Biobank, FinnGen, and the International Multiple Sclerosis Genetics Consortium (IMSGC).
Results: The study included 838 SNPs for all risk factors, with sample sizes ranging from 23,205 to 607,291 per risk factor, obtained from various consortia. The results showed that in the IMSGC consortium, a genetic predisposition to vitamin D was significantly associated with a 33% lower risk of MS (OR = 0.67, p = 0.05). In contrast, there would be a 1-SD rise in the odds of MS for each increase in genetically estimated BMI and low-density lipoprotein (LDL) (OR = 1.31, p = 0.05, and OR=1.11, p = 0.05, respectively).
Conclusion: This study suggested that vitamin D level, BMI, and LDL might be causally related to the development of MS. These findings might have significant implications for the advancement of MS preventive and therapeutic strategies.
Key words: Multiple sclerosis, Mendelian randomization, vitamin D, BMI, LDL.
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