Investigating the potential effect of topiramate on anorexia nervosa and binge eating behaviour using drug-target Mendelian randomization

Genetically predicted inhibition of CA4 expression in blood is linked to lower binge-eating behaviour risk (OR = 0.867, 95% CI = 0.792–0.950, p = 0.002) in a large case-control dataset.

• Why it matters: It is unclear whether topiramate’s pharmacological effects on appetite suppression and weight loss translate into altered eating-disorder risk, leaving a key mechanism gap.
• What they did: Using drug-target Mendelian randomization with summary-data-based MR, the study validated five instruments for topiramate’s antiepileptic action via brain- and blood-derived cis-eQTLs for target genes, then tested anorexia nervosa and binge-eating behaviour.
• The result: After multiple-testing correction, the CA4 blood signal remained significant in SMR-multi (p = 0.0049) with moderate colocalization support (PPH4 = 0.58), while no robust evidence emerged for anorexia nervosa or eight other psychiatric outcomes.

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