medRxiv PreprintsInternational9 November 2026
Neurotransmitter-specific polygenic scores dissect clinical heterogeneity in schizophrenia
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Schizophrenia (SCZ) is a highly heritable psychiatric disorder characterised by substantial clinical heterogeneity. While global polygenic scores (gPGS) capture genetic liability to SCZ, their ability to explain clinical variability remains limited. Pathway-stratified polygenic scores (sPGS) offer a biologically informed approach to patient stratification. In this study, common genetic variants were annotated across five neurotransmitter (NT) signalling pathways - acetylcholine (ACh), dopamine, gamma-aminobutyric acid (GABA), glutamate (Glu), and serotonin. sPGS adjusted for sex and ancestry p
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