Toulopoulou Timothea, Goldberg Terry E, Mesa Irene Rebollo, Picchioni Marco, Rijsdijk Fruhling, Stahl Daniel, Cherny Stacey S, Sham Pak, Faraone Stephen V, Tsuang Ming, Weinberger Daniel R, Seidman Larry J, Murray Robin M
King's College London, United Kingdom.
Arch Gen Psychiatry. 2010 Sep;67(9):905-13. doi: 10.1001/archgenpsychiatry.2010.99.
The DSM-IV concept of schizophrenia offers diagnostic reliability but etiologic and pathologic heterogeneity, which probably contributes to the inconsistencies in genetic studies. One solution is to identify intermediate phenotypes, "narrower" constructs of liability, that hypothetically share genetic risk with the disorder. Although a variety of candidate intermediate phenotypes have emerged, few have explicitly quantified the extent of their genetic overlap with schizophrenia.
To quantify the net-shared genetic effects between schizophrenia and specific cognitive candidate intermediate phenotypes.
Twin and family design.
Adult psychiatric research centers in the United States and the United Kingdom.
A total of 2056 participants: 657 patients with schizophrenia, 674 first-degree relatives (including co-twins), and 725 controls.
(1) Latent factors capturing the common variance between cognitive tasks, (2) separation of the latent factors into their genetic and environmental components, and (3) estimation of the net-shared genetic variance between the latent cognitive factors or intelligence and schizophrenia.
Genetic factors contributed substantially to the total variance in cognition (immediate recall latent factor: 0.66; 95% confidence interval [CI], 0.62 to 0.85; delayed recall latent factor: 0.48; 0.42 to 0.55; and intelligence: 0.66; 0.62 to 0.71). The latent common factors for modality-specific immediate and delayed recall and intelligence showed similar levels of phenotypic covariance with schizophrenia (immediate recall: -0.35; delayed recall: -0.37; and intelligence: -0.38), with 72%, 86%, and 89%, respectively, due to shared genetic effects with schizophrenia. Environmental effects accounted for little phenotypic correlation between cognition and schizophrenia.
Using the largest international familial schizophrenia cohort to date, we showed that a substantial portion of the phenotypic correlation between schizophrenia and cognition is caused by shared genetic effects. However, because the phenotypic and genetic correlations are far from unity, the genetics of schizophrenia are clearly not merely the genetics of cognition.
《精神疾病诊断与统计手册》第四版（DSM-IV）中精神分裂症的概念提供了诊断可靠性，但存在病因和病理异质性，这可能导致了基因研究结果的不一致。一种解决办法是识别中间表型，即“更狭义”的易感性结构，假设其与该疾病共享遗传风险。尽管已经出现了多种候选中间表型，但很少有研究明确量化它们与精神分裂症的遗传重叠程度。
量化精神分裂症与特定认知候选中间表型之间的净共享遗传效应。
双生子和家系设计。
美国和英国的成人精神病学研究中心。
共2056名参与者，其中657名精神分裂症患者、674名一级亲属（包括双胞胎）和725名对照。
（1）捕捉认知任务间共同方差的潜在因子；（2）将潜在因子分离为遗传和环境成分；（3）估计潜在认知因子或智力与精神分裂症之间的净共享遗传方差。
遗传因素对认知的总方差有很大贡献（即时回忆潜在因子：0.66；95%置信区间[CI]，0.62至0.85；延迟回忆潜在因子：0.48；0.42至0.55；智力：0.66；0.62至0.71）。特定模态即时和延迟回忆以及智力的潜在共同因子与精神分裂症表现出相似水平的表型协方差（即时回忆：-0.35；延迟回忆：-0.37；智力：-0.38），分别有72%、86%和89%归因于与精神分裂症的共享遗传效应。环境效应在认知与精神分裂症之间的表型相关性中占比很小。
使用迄今为止最大的国际精神分裂症家系队列，我们发现精神分裂症与认知之间的很大一部分表型相关性是由共享遗传效应引起的。然而，由于表型和遗传相关性远未达到统一，精神分裂症的遗传学显然不仅仅是认知的遗传学。
