Obesity and Multiple Sclerosis: A Mendelian Randomization Study.

observational studies have reported an association between obesity, as measured by an increase in body mass index (BMI), in early adulthood and the risk of multiple sclerosis (MS). However, the potential bias introduced by confounding and reverse causation may have influenced these findings. Therefore, we chose to do a Mendelian randomization (MR) analysis to evaluate whether increased BMI was associated with increased genetic risk of MS.

Using the approach MR two samples, we use a statistical summary of the Genetic Investigation of Anthropometric Traits (GIANT) consortium and the Consortium of MS Genetics International (IMSGC), the study of genome-wide association site for BMI and MS, respectively (GIANT: n = 322 105; IMSGC: n = 14 498 cases and 24 091 controls). Seventy-one-nucleotide polymorphisms (SNPs) whose genome was significant (p <5 x 10-8) for BMI at GIANT (n = 322 105) and investigated for their association with the risk of MS in IMSGC.

The effect of each SNP in MS weighed against the effect on BMI, and estimates compiled to provide a summary measure of the effect of increased BMI on the risk of MS. Our results suggest that increased BMI affects MS susceptibility, where 1 standard deviation increase in genetically determined BMI (kg / m2) increased likelihood of MS by 41% (odds ratio [OR]: 1.41, 95% CI 1.20 to 1 , 66, p = 2.7 x 10-5, I2 = 0%, 95% CI 0-29). A sensitivity analysis, including MR-Egger regression and weighted median approach provided no evidence of pleiotropic effects. The main limitation of the study is that, while this sensitivity analysis reduces the likelihood that pleiotropy influenced our results, the rest of pleiotropy is difficult to exclude completely.

BMI is associated with an elevated genetic risk of MS, providing evidence for the causal role of obesity in MS etiology. While obesity has been associated with a lot of late-life outcomes, these findings suggest important consequence of childhood and / or early adulthood obesity

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