Genetic risk, antiseizure medications, and lifestyle factors in epilepsy-associated obesity and overweight
Authors' conclusion
Genetic predisposition, ASMs, and lifestyle behaviours were collectively associated with the risk of overweight and obesity in epilepsy. LTG use was associated with a lower risk of weight gain, particularly among individuals with lower genetic susceptibility, with this association attenuating as genetic risk for obesity increased. VPA was associated with an increased risk of obesity, especially in females. These findings support personalised metabolic risk management in epilepsy care.
Study context
- Population
- UK Biobank participants with epilepsy recruited 2006–2010, classified into low, medium and high genetic risk by PRS for BMI
- Participants
- 8,451 participants
- Exposure
- ASM use vs non-use, by PRS for BMI
- Outcome
- Overweight/obesity
Methodological detailsUK Biobank, multivariable logistic regression, Mendelian randomisation
- UK Biobank
- Multivariable logistic regression
- Mendelian randomisation
Main finding
As reported in the abstract
Observational data: associations, not effects.
Further findings
Obesity/overweight by PRS for BMI subgroup
- Lamotrigine (LTG) use associated with lower obesity risk, particularly with low to moderate PRS for BMI; absolute difference in overweight risk between LTG users and non-users decreased as PRS for BMI increased
Sex-stratified analyses
- LTG had a more substantial protective effect in males; Valproate (VPA) more strongly associated with obesity risk in females
Lifestyle factors
- Higher physical activity and adherence to a healthy diet associated with lower obesity and overweight risk
Mendelian randomisation (MR): LTG target gene expression and BMI
- Potential causal relationship between LTG target gene expression and BMI
Original publication
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