Importance Schizophrenia is a clinically heterogeneous disorder. It is currently unclear how variability in symptom dimensions and cognitive ability is associated with genetic liability for schizophrenia. Objective To determine whether phenotypic dimensions within schizophrenia are associated with genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence. Design, Setting, and Participants In a genetic association study, 3 cross-sectional samples of 1220 individuals with a diagnosis of schizophrenia were recruited from community, inpatient, and voluntary sector mental health services across the UK. Confirmatory factor analysis was used to create phenotypic dimensions from lifetime ratings of the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and the MATRICS Consensus Cognitive Battery. Analyses of polygenic risk scores (PRSs) were used to assess whether genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence were associated with these phenotypic dimensions. Data collection for the cross-sectional studies occurred between 1993 and 2016. Data analysis for this study occurred between January 2019 and March 2021. Main Outcomes and Measures Outcome measures included phenotypic dimensions defined from confirmatory factor analysis relating to positive symptoms, negative symptoms of diminished expressivity, negative symptoms of motivation and pleasure, disorganized symptoms, and current cognitive ability. Exposure measures included PRSs for schizophrenia, bipolar disorder, major depression, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intelligence. Results Of the 1220 study participants, 817 were men (67.0%). Participants' mean (SD) age at interview was 43.10 (12.74) years. Schizophrenia PRS was associated with increased disorganized symptom dimension scores in both a 5-factor model (β = 0.14; 95% CI, 0.07-0.22; P = 2.80 × 10-4) and a 3-factor model across all samples (β = 0.10; 95% CI, 0.05-0.15; P = 2.80 × 10-4). Current cognitive ability was associated with genetic liability to schizophrenia (β = -0.11; 95% CI, -0.19 to -0.04; P = 1.63 × 10-3) and intelligence (β = 0.23; 95% CI, 0.16-0.30; P = 1.52 × 10-10). After controlling for estimated premorbid IQ, current cognitive performance was associated with schizophrenia PRS (β = -0.08; 95% CI, -0.14 to -0.02; P = 8.50 × 10-3) but not intelligence PRS. Conclusions and Relevance The findings of this study suggest that genetic liability for schizophrenia is associated with higher disorganized dimension scores but not other symptom dimensions. Cognitive performance in schizophrenia appears to reflect distinct contributions from genetic liabilities to both intelligence and schizophrenia.

中文翻译：

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精神分裂症多基因责任、症状维度和精神分裂症认知能力之间的关联。

重要性精神分裂症是一种临床异质性疾病。目前尚不清楚症状维度和认知能力的变异性如何与精神分裂症的遗传易感性相关。目的 确定精神分裂症的表型维度是否与精神分裂症、其他神经精神疾病和智力的遗传易感性相关。设计、设置和参与者 在一项遗传关联研究中，从英国各地的社区、住院病人和志愿部门的心理健康服务机构招募了 1220 名被诊断为精神分裂症的个体的 3 个横断面样本。验证性因子分析用于从阳性症状评估量表、阴性症状评估量表、和 MATRICS 共识认知电池。多基因风险评分 (PRS) 分析用于评估对精神分裂症、其他神经精神疾病和智力的遗传易感性是否与这些表型维度相关。横断面研究的数据收集发生在 1993 年至 2016 年之间。本研究的数据分析发生在 2019 年 1 月至 2021 年 3 月之间。主要结果和措施 结果措施包括与阳性症状相关的确认性因素分析定义的表型维度，减少的阴性症状表达能力、动机和快乐的负面症状、杂乱无章的症状和当前的认知能力。暴露措施包括针对精神分裂症、双相情感障碍、重度抑郁症、注意力缺陷/多动障碍、自闭症谱系障碍、和智力。结果 在 1220 名研究参与者中，817 名是男性（67.0%）。受访者的平均 (SD) 年龄为 43.10 (12.74) 岁。在 5 因子模型（β = 0.14；95% CI，0.07-0.22；P = 2.80 × 10-4）和所有样本的 3 因子模型（β = 0.10；95% CI，0.05-0.15；P = 2.80 × 10-4)。目前的认知能力与精神分裂症的遗传易感性相关（β = -0.11；95% CI，-0.19 至 -0.04；P = 1.63 × 10-3）和智力（β = 0.23；95% CI，0.16-0.30；P = 1.52 × 10-10)。在控制估计的病前智商后，当前的认知表现与精神分裂症 PRS 相关（β = -0.08；95% CI，-0.14 至 -0.02；P = 8.50 × 10-3），但与智力 PRS 无关。结论和相关性 本研究的结果表明，精神分裂症的遗传责任与较高的无序维度得分相关，但与其他症状维度无关。精神分裂症的认知表现似乎反映了遗传倾向对智力和精神分裂症的不同贡献。