ABSTRACT Introduction Genetic factors are thought to play an important role in antipsychotic‐induced weight gain (AIWG). Polygenic risk scores (PRS) could provide a measure of genetic predisposition to antipsychotic drug induced weight gain (AIWG).We conducted a study to examine how a PRS, generated using SNPs, identified from a recent meta‐analysis, related to weight‐change over time in people with first episode‐psychosis. Methods The PRS included SNPs in six different genes, identified as having significant associations ( p 7%) was investigated using regression models. Results In multiple regression analysis, the additive PRS significantly predicted AIWG in females (adjusted r 2 = 0.59, B: unstandardised regression coefficient = 24.4 g/day p < 0.05), but not in males. ANCOVA showed that high genetic risk groups had greater WGPD ( p = 0.018), with significant PRS gender interactions driven by markedly higher WGPD in high‐risk females ( p = 0.039). None of the models tested were associated with BMI percentage change. Conclusion We report a PRS that is predictive of weight gain in women treated for first episode psychosis, accounting for 59% of the variance daily weight‐gain over time. Validation in an independent cohort is required, as is determining whether it is feasible to apply the PRS prospectively.
Heald et al. (Sun,) studied this question.