Centre for Genetic Origins of Health and Disease, Faculty of Medicine, Dentistry & Health Sciences, The University of Western Australia and Faculty of Health Sciences, Curtin University, Perth, Australia.
Centre for Clinical Research in Neuropsychiatry, Division of Psychiatry, Medical School, University of Western Australia, Perth, Australia.
Schizophr Bull. 2018 Jun 6;44(4):908-921. doi: 10.1093/schbul/sbx141.
Phenotypic heterogeneity is a major barrier to understanding the genetic architecture underlying schizophrenia. Incorporating endophenotypes is one way to reduce heterogeneity and facilitate more powerful genetic analysis. Candidate endophenotypes require systematic assessment against endophenotype criteria, and a ranking of their potential utility for genetic analysis. In this study we assess 20 cognitive and personality measures in a sample of 127 families with at least 2 cases of schizophrenia per family (n = 535) plus a set of 30 control families (n = 121) against 4 endophenotype criteria: (a) be associated with the illness but not be a part of its diagnosis, (b) be heritable, (c) co-segregate with the illness in families, and (d) be found in unaffected relatives at a higher rate than in the general population. The endophenotype ranking score (endophenotype ranking variable [ERV]) was used to rank candidate endophenotypes based on their heritability and genetic correlation with schizophrenia. Finally, we used factor analysis to explore latent factors underlying the cognitive and personality measures. Evidence for personality measures as endophenotypes was at least equivalent to that of the cognitive measures. Factor analysis indicated that personality and cognitive traits contribute to independent latent dimensions. The results suggest for this first time that a number of cognitive and personality measures are independent and informative endophenotypes. Use of these endophenotypes in genetic studies will likely improve power and facilitate novel aetiological insights.
表型异质性是理解精神分裂症遗传结构的主要障碍。纳入内表型是减少异质性和促进更强大的遗传分析的一种方法。候选内表型需要根据内表型标准进行系统评估，并对其用于遗传分析的潜在效用进行排名。在这项研究中，我们评估了 127 个至少有 2 例精神分裂症病例的家庭样本（n = 535）中的 20 项认知和人格测量，以及一组 30 个对照家庭（n = 121），以评估它们是否符合 4 个内表型标准：（a）与疾病相关，但不是其诊断的一部分，（b）可遗传，（c）在家庭中与疾病共分离，（d）在未受影响的亲属中比在普通人群中更常见。内表型评分（内表型评分变量 [ERV]）用于根据遗传力和与精神分裂症的遗传相关性对内表型候选物进行排名。最后，我们使用因子分析探索认知和人格测量背后的潜在因素。人格测量作为内表型的证据至少与认知测量相当。因子分析表明，人格和认知特征有助于独立的潜在维度。结果表明，首次有一些认知和人格测量是独立且信息丰富的内表型。在遗传研究中使用这些内表型可能会提高功效，并促进新的病因学见解。
