Genetic Risk and Resilience for Schizophrenia Stratified by Perinatal Gene Expression Predict Adult Cognitive Performance
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Genetic risk for schizophrenia (SCZ) has been linked to cognitive performance before the onset age. We examined how SCZ-related polygenic risk and resilience variants, and their co-expression patterns in the human brain, were associated with cognitive abilities across development in 16,520 non-psychiatric European and African ancestry children and adults. SCZ risk showed significant negative associations with spatial, verbal, and working memory across ancestries (all t<-2, pFDR<0.05). In Europeans, risk and resilience variants had opposing effects on attention, working and spatial memory (Δt>4, pFDR<0.05). Polygenic scores filtered through perinatal co-expression networks showed stronger links with cognition than adult (ΔAIC>5.75, p=0.02) or juvenile (ΔAIC>5.8, p=0.03) networks. Cross-ancestry correlations (R=0.52, p<0.01) highlight replicability. These findings support the neurodevelopmental basis of SCZ, suggesting that risk and resilience variants influence cognition from early life, independent of symptoms and elucidate biological pathways through which SCZ risk may influence early cognitive development.
