National Center for Geriatrics and Welfare Research, National Health Research Institutes, Zhunan, Taiwan.
College of Public Health, China Medical University, Taichung, Taiwan.
Transl Psychiatry. 2024 Nov 16;14(1):472. doi: 10.1038/s41398-024-03182-6.
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) and BPD (PRS), shared PRS between SCZ and BPD (PRS), and SCZ-specific PRS (PRS). Based on the sign-concordance of the susceptibility variants with SCZ/BPD, PRS was split into PRS/PRS, and PRS was split into PRS/PRS. 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 PRS, and PRS were positively associated with educational attainment, whereas PRS was negatively associated with educational attainment. PRS was negatively associated with MMSE, while PRS was positively associated with MMSE. The concordant and discordant parts of polygenic liabilities have contrasting association, PRS and PRS mainly determined these effects mentioned above PRS 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.
为了阐明精神分裂症（SCZ）和双相情感障碍（BPD）的特定和共同遗传背景，本研究探讨了 SCZ 和 BPD 的多基因风险与受教育程度和认知衰老的关联。在来自台湾生物库的 106806 名无血缘关系的社区参与者中，我们计算了 SCZ 的多基因风险评分（PRS）（PRS）和 BPD 的多基因风险评分（PRS）（PRS）、SCZ 和 BPD 之间的共享 PRS（PRS）以及 SCZ 特异性 PRS（PRS）。根据与 SCZ/BPD 易感性变异的符号一致性，将 PRS 分为 PRS/PRS，将 PRS 分为 PRS/PRS。使用有序逻辑回归模型来估计与受教育程度的关联。使用线性回归模型来估计与认知衰老（n=27005）的关联，认知衰老用 Mini-Mental State Examination（MMSE）测量，并估计年龄≥60 岁的个体中 MMSE 变化（n=6194，平均随访时间为 3.9 年）的关联。PRS PRS 和 PRS 与受教育程度呈正相关，而 PRS 与受教育程度呈负相关。PRS 与 MMSE 呈负相关，而 PRS 与 MMSE 呈正相关。多基因风险的一致和不一致部分具有相反的关联，PRS 和 PRS 主要决定了上述这些效应，PRS 预测 MMSE 评分的降低。利用大量社区样本，本研究为 SCZ 和 BPD 多基因结构对受教育程度和认知衰老的对比影响提供了证据，并表明 SCZ 和 BPD 在遗传上并非同质。
