Basal metabolic rate and risk of multiple sclerosis: a Mendelian randomization study

To determine the relationship between basal metabolic rate (BMR) and multiple sclerosis (MS) susceptibility, we analyzed genome-wide association study (GWAS) summary statistics data from the International Multiple Sclerosis Genetics Consortium on a total of 115,803 participants of European descent, including 47,429 patients with MS and 68,374 controls. We selected 378 independent genetic variants strongly associated with BMR in a GWAS involving 454,874 participants as instrumental variables to examine a potential causal relationship between BMR and MS. A genetically predicted higher BMR was associated with a greater risk of MS (odds ratio [OR]: 1.283 per one standard deviation increase in BMR, 95% confidence interval [CI]: 1.108-1.486, P = 0.001). Moreover, we used the lasso method to eliminate heterogeneity (Q statistic = 384.58, P = 0.370). There was no pleiotropy in our study and no bias was found in the sensitivity analysis using the leave-one-out test. We provide novel evidence that a higher BMR is an independent causal risk factor in the development of MS. Further work is warranted to elucidate the potential mechanisms.