BACKGROUND Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases. METHODS We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases. RESULTS PRS for both population IQ (P = 4.39 × 10-28) and EA (P = 1.27 × 10-26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS. CONCLUSIONS Cognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.

中文翻译：

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精神分裂症的多基因风险评分与认知之间的关系。

背景技术认知障碍是精神分裂症的临床重要特征。多基因风险评分（PRS）方法已证明精神分裂症，双相情感障碍（BD），重度抑郁症（MDD），教育程度（EA）和智商之间存在遗传重叠，但很少有研究检查这些PRS与认知表型之间的关联精神分裂症病例。方法我们将11份样本中的3034例精神分裂症患者的遗传和认知数据结合起来，以通用智力因子g作为认知的主要指标。我们使用线性回归检查了EA，IQ，精神分裂症，BD和MDD的认知与PRS之间的关联。然后对所有样品进行荟萃分析。在精神分裂症病例中进行了认知的全基因组关联研究（GWAS）。结果精神分裂症患者的智商（P = 4.39×10-28）和EA（P = 1.27×10-26）的PRS与认知呈正相关。相比之下，精神分裂症患者的认知与精神分裂症的PRS（P = .39），BD（P = .51）或MDD（P = .49）之间没有关联。在GWAS中，没有任何个体变异达到全基因组意义。结论精神分裂症患者的认知与PRS关联更紧密，PRS与一般精神疾病患者的PRS相比，PRS反映了一般人群的认知特征。这表明精神分裂症内认知变异的机制至少部分独立于易患精神分裂症诊断本身的机制。