Family health history and pharmacogenomics show cross generation premature amitriptyline discontinuation is associated with CYP2C19 loss of-function enrichment.

backgroundGenetics influence medication response yet integrating family health history (FHH) of medication response with pharmacogenomics remains underexplored. The objective of this study was to examine cross-generational medication exposure patterns and assess the utility of FHH for medication response using electronic health records.

methodsGenes & Health (G&H) data from Bangladeshi and Pakistani participants were analysed for parent-offspring trios with medication exposure. Premature discontinuation of amitriptyline was defined as discontinuation within three months. Logistic regression and Fisher's exact test explored the relationship between parental discontinuation, offspring discontinuation, and CYP2C19 loss-of-function variants.

results13% of offspring prescriptions overlap with parental prescriptions, primarily short-term treatments (antibiotics, vaccines, steroids). In 96 trios, cross-generational amitriptyline exposure is observed. Parental discontinuation does not predict offspring discontinuation (p = 0.275, OR 1.70). However, offspring with two-generation histories of early discontinuation are significantly enriched for CYP2C19 predicted poor metabolizers (38% vs. 10.5%, p = 0.049, OR 4.86).

conclusionsFHH of medication response can highlight individuals enriched for pharmacogenomic variants. This is a clinically useful finding, which may flag psychiatric patients with a two-generation history of early amitriptyline discontinuation or intolerance as a priority for pharmacogenomic testing. This study demonstrates the potential of integrating FHH into clinical pharmacogenomics for actionable insights.