A systematic review of Mendelian randomization studies on multiple sclerosis

Area of Science:

• Epidemiology
• Genetics
• Neurology

Background:

• Multiple sclerosis (MS) is a complex disease with suspected genetic and environmental influences.
• Observational studies suggest links between modifiable factors and MS risk but are limited by confounding and reverse causation.
• Mendelian randomization (MR) offers a robust method to infer causality using genetic variants.

Approach:

• Systematic review of MR studies investigating causal effects on MS risk.
• Inclusion of studies using genome-wide association study (GWAS) summary-level data.
• Qualitative synthesis of eligible studies to identify key risk factors.

Key Points:

• MR analysis strengthens causal inference for disease risk factors.
• Low vitamin D levels were identified as a significant risk factor for increased MS risk.
• High adult body mass index (BMI) was also confirmed as a causal risk factor for MS.

Conclusions:

• Mendelian randomization provides reliable causal conclusions for MS etiology.
• Low vitamin D and high BMI are established causal risk factors for multiple sclerosis.
• MR studies utilizing GWAS data are crucial for pinpointing modifiable exposures impacting complex diseases.