Polygenic signal for symptom dimensions and cognitive performance in patients with chronic schizophrenia

We found a significant effect of PRS on positive symptoms at p-threshold (PT) of 0.5 (R2 = 0.007, p = 0.029, empirical p = 0.029) and negative symptoms at PT of 1e-07 (R2 = 0.005, p = 0.047, empirical p = 0.048). For models that additionally controlled for neurocognition, best fit PRS predicted positive (p-threshold 0.01, R2 = 0.007, p = 0.013, empirical p = 0.167) and negative symptoms (p-threshold 0.1, R2 = 0.012, p = 0.004, empirical p = 0.329). No associations were seen for overall neurocognitive and social cognitive performance tests. Post-hoc analyses revealed that PRS predicted working memory and vigilance performance but did not survive correction. No candidate regions that survived multiple testing corrections were associated with either symptoms or cognitive performance. Our findings point to potentially distinct pathogenic mechanisms for schizophrenia symptoms.