精神分裂症是一种与广泛的认知障碍相关的多因素疾病。尽管认知缺陷是与精神分裂症(SZ)功能障碍最密切相关的因素之一,目前的治疗策略很难解决这些障碍。为患者制定更有效的治疗策略,需要更好地了解它们的发病机制。遗传学的最新进展,由大型全基因组关联研究(GWAS)和多基因风险评分(PRS)的使用驱动,提供了关于复杂人类特征遗传结构的新见解,包括认知和SZ。这里,我们回顾了最近在基于人群的样本以及SZ参与者中检验SZ与认知功能之间遗传联系的研究结果.进行的荟萃分析显示,当样本依赖于一般和健康参与者时,精神分裂症的多遗传风险评分与整体认知之间呈负相关(p<0.001)。而三项针对精神分裂症患者的研究进行荟萃分析时,没有发现显著的相关性(p>0.05)。因此,我们的综述和荟萃分析反对精神分裂症等位基因和认知的普遍多效性,因为SZ患者的认知能力将受到与普通人群相同的遗传因素的支持,并且基本上独立于该疾病的常见变体责任。
Schizophrenia is a multifactorial disease associated with widespread cognitive impairment. Although cognitive deficits are one of the factors most strongly associated with functional impairment in schizophrenia (SZ), current treatment strategies hardly tackle these impairments. To develop more efficient treatment strategies in patients, a better understanding of their pathogenesis is needed. Recent progress in genetics, driven by large genome-wide association studies (GWAS) and the use of polygenic risk scores (PRS), has provided new insights about the genetic architecture of complex human traits, including cognition and SZ. Here, we
review the recent findings examining the genetic links between SZ and cognitive functions in population-based samples as well as in participants with SZ. The performed meta-analysis showed a negative correlation between the polygenetic risk score of schizophrenia and global cognition (p < 0.001) when the samples rely on general and healthy participants, while no significant correlation was detected when the three studies devoted to schizophrenia patients were meta-analysed (p > 0.05). Our
review and meta-analysis therefore argues against universal pleiotropy for schizophrenia alleles and cognition, since cognition in SZ patients would be underpinned by the same genetic factors than in the general population, and substantially independent of common variant liability to the disorder.