Abstract
To elucidate the specific and shared genetic background of schizophrenia (SCZ) and bipolar disorder (BPD), this study explored the association of polygenic liabilities for SCZ and BPD with educational attainment and cognitive aging. Among 106,806 unrelated community participants from the Taiwan Biobank, we calculated the polygenic risk score (PRS) for SCZ (PRS(SCZ)) and BPD (PRS(BPD)), shared PRS between SCZ and BPD (PRS(SCZ+BPD)), and SCZ-specific PRS (PRS(SCZvsBPD)). Based on the sign-concordance of the susceptibility variants with SCZ/BPD, PRS(SCZ) was split into PRS(SCZ_concordant)/PRS(SCZ_discordant), and PRS(BPD) was split into PRS(BPD_concordant)/PRS(BPD_discordant). Ordinal logistic regression models were used to estimate the association with educational attainment. Linear regression models were used to estimate the associations with cognitive aging (n = 27,005), measured by the Mini-Mental State Examination (MMSE), and with MMSE change (n = 6194 with mean follow-up duration of 3.9 y) in individuals aged≥ 60 years. PRS(SCZ,) PRS(BPD), and PRS(SCZ+BPD) were positively associated with educational attainment, whereas PRS(SCZvsBPD) was negatively associated with educational attainment. PRS(SCZ) was negatively associated with MMSE, while PRS(BPD) was positively associated with MMSE. The concordant and discordant parts of polygenic liabilities have contrasting association, PRS(SCZ_concordant) and PRS(BPD_concordant) mainly determined these effects mentioned above(.) PRS(SCZvsBPD) predicted decreases in the MMSE scores. Using a large collection of community samples, this study provided evidence for the contrasting effects of polygenic architecture in SCZ and BPD on educational attainment and cognitive aging and suggested that SCZ and BPD were not genetically homogeneous.