Genetic Association and Causal Effects Between Obesity and Multiple Sclerosis: A Robust Two-Sample Mendelian...

Area of Science:

• Neuroepidemiology
• Genetic Epidemiology
• Public Health

Background:

• Observational studies suggest a link between obesity (measured by BMI) and multiple sclerosis (MS).
• The causal nature of this association requires further investigation.
• Mendelian randomization (MR) offers a robust approach to infer causality.

Purpose of the Study:

• To investigate the potential causal relationship between body mass index (BMI) and the risk of developing multiple sclerosis (MS).
• To utilize a two-sample Mendelian randomization (MR) approach for robust causal inference.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data for BMI and MS.
• Employed multiple analytical methods including Inverse-Variance Weighted (IVW), Weighted Median, and MR-Egger.
• Assessed heterogeneity and horizontal pleiotropy using Cochran's Q-test and MR-Egger intercept; sensitivity analyses confirmed robustness.

Main Results:

• A significant causal effect of increased BMI on the risk of MS was observed across multiple MR methods (e.g., IVW OR=1.39, P=1.42e-07).
• No significant evidence of heterogeneity or horizontal pleiotropy was detected, supporting the validity of the findings.
• Sensitivity analyses, including MR-PRESSO and MR-RAPS, confirmed the robustness of the causal association.

Conclusions:

• This study provides strong evidence that higher body mass index (BMI) causally increases the risk of developing multiple sclerosis (MS).
• Maintaining a healthy body weight, particularly during early life, may be a potential preventative strategy for reducing MS risk.
• Findings underscore the importance of weight management in public health initiatives targeting neurological disorders.