Genetic causal association between physical activities and epilepsy: A Mendelian randomization study

Area of Science:

• Neurology
• Genetics
• Epidemiology

Background:

• The relationship between physical activity (PA) and epilepsy remains debated.
• Causality between PA and epilepsy requires robust investigation.

Purpose of the Study:

• To investigate the potential causal effect of physical activity on epilepsy using Mendelian randomization (MR).
• To differentiate the impact of objectively measured versus self-reported physical activity on epilepsy risk.

Main Methods:

• Utilized two-sample MR with genetic variants for overall acceleration average (OAA), moderate, and vigorous physical activities (MPA/VPA).
• Assessed five epilepsy subtypes as outcomes.
• Employed inverse-variance weighted (IVW) as the primary method, with sensitivity analyses.

Main Results:

• Overall acceleration average (OAA) showed a genetic association with reduced risk of focal epilepsy (IVW, p=0.015) and focal epilepsy-strict definition (IVW, p=0.003; Weighted median, p=0.035).
• No significant causal associations were found for genetically predicted MPA or VPA with any epilepsy subtype.
• No evidence of heterogeneity, pleiotropy, or significant outliers was detected.

Conclusions:

• Objectively measured physical activity (via accelerometry) may lower the risk of developing focal epilepsy.
• Self-reported physical activity levels (MPA, VPA) do not demonstrate a causal link to epilepsy.
• Distinguishes the potential protective effects of objectively measured PA from self-reported PA in epilepsy.