The genetic relationship between educational attainment and cognitive performance in major psychiatric disorders
The genetic relationship between educational attainment and cognitive performance in major psychiatric disorders
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DOI：
10.1038/s41398-019-0547-x
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发表时间：
2019-08-28
影响因子：
6.8
通讯作者：
Papiol, Sergi
中科院分区：
文献类型：
--
作者：
Comes, Ashley L.;Senner, Fanny;Papiol, Sergi
认知缺陷是精神分裂症和双相情感障碍等精神疾病的核心特征。证据支持全基因组多基因评分（GPS）的教育程度（GPS(EDu)）可用于解释认知表现的变异性。我们的目的是在已知认知缺陷的慢性精神病患者的跨诊断临床队列中确定与GPS（EDu）相关的不同认知域。研究对象为PsyCourse队列中的双相情感障碍和精神分裂症患者（N= 730, 43%为女性）。同样，我们测试了精神分裂症（GPS(sz)）和双相情感障碍（GPS(BD)）的GPS是否与认知结果相关。GPS（EDu）解释了1.5%的反向文字数字广度差异、1.9%的文字学习与记忆测试中正确回忆的单词数量差异和1.1%的结晶智力差异。这些效应不受治疗和诊断的影响。GPS（sz）或GPS（BD）与认知结果无显著关联。此外，这些风险评分并没有混淆GPS（EDu）对认知结果的影响。GPS（EDu）解释了一小部分患有精神疾病的成年人的认知表现，特别是与语言学习和工作记忆相关的领域。对这种代用表型进行纵向研究，可以对疾病过程提供有趣的见解，突出基因在什么时候对认知表现发挥更大的影响。更好地了解这些缺陷的起源可能有助于识别那些有较低功能水平和不良社会结果风险的患者。多基因估计可能在未来成为预测模型的一部分，用于更个性化的干预。
Cognitive deficits are a core feature of psychiatric disorders like schizophrenia and bipolar disorder. Evidence supports a genome-wide polygenic score (GPS) for educational attainment (GPS(EDu)) can be used to explain variability in cognitive performance. We aimed to identify different cognitive domains associated with GPS(EDu) in a transdiagnostic clinical cohort of chronic psychiatric patients with known cognitive deficits. Bipolar and schizophrenia patients from the PsyCourse cohort (N= 730; 43% female) were used. Likewise, we tested whether GPSs for schizophrenia (GPS(sz)) and bipolar disorder (GPS(BD)) were associated with cognitive outcomes. GPS(EDu) explained 1.5% of variance in the backward verbal digit span, 1.9% in the number of correctly recalled words of the Verbal Learning and Memory Test, and 1.1% in crystallized intelligence. These effects were robust to the influences of treatment and diagnosis. No significant associations between GPS(sz) or GPS(BD )with cognitive outcomes were found. Furthermore, these risk scores did not confound the effect of GPS(EDu) on cognitive outcomes. GPS(EDu) explains a small fraction of cognitive performance in adults with psychiatric disorders, specifically for domains related to linguistic learning and working memory. Investigating such a proxy-phenotype longitudinally, could give intriguing insight into the disease course, highlighting at what time genes play a more influential role on cognitive performance. Better understanding the origin of these deficits might help identify those patients at risk for lower levels of functioning and poor social outcomes. Polygenic estimates may in the future be part of predictive models for more personalized interventions.