University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands; University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center, Groningen, the Netherlands.
University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center, Groningen, the Netherlands.
Schizophr Res. 2020 Sep;223:135-147. doi: 10.1016/j.schres.2020.05.020. Epub 2020 Jul 4.
Cross-sectional studies have shown that the polygenic risk score for schizophrenia (PRS) may influence heterogeneity in cognitive performance although evidence from family-based longitudinal study is limited. This study aimed to identify trajectories of cognitive function and assess whether the PRS is associated with baseline cognitive performance and predicted six-year trajectories. We included 1119 patients with a schizophrenia spectrum disorder, and 1059 unaffected siblings and 586 unrelated controls who are eligible at baseline. Genotype data were collected at baseline, whereas clinical and sociodemographic data were collected at baseline, three and six years. Group-based trajectory modeling was applied on a weighted standardized composite score of general cognition to unravel cognitive subtypes and explore trajectories over time. We followed a standard procedure to calculate the polygenic risk score. A random-effects ordinal regression model was used to investigate the association between PRS and cognitive subtypes. Five cognitive subtypes with variable trajectories were found in patients, four in siblings and controls, and six in all combined samples. PRS significantly predicted poor cognitive trajectories in patients, siblings and all samples. After Bonferroni correction and adjustment for non-genetic factors, only the results in all combined sample remained significant. Cognitive impairment in schizophrenia is heterogeneous and may be linked with high PRS. Our finding confirmed at least in all combined samples the presence of genetic overlap between schizophrenia and cognitive function and can give insight into the mechanisms of cognitive deficits.
横断面研究表明，精神分裂症的多基因风险评分（PRS）可能会影响认知表现的异质性，尽管来自基于家庭的纵向研究的证据有限。本研究旨在确定认知功能的轨迹，并评估 PRS 是否与基线认知表现相关，并预测六年的轨迹。我们纳入了 1119 名精神分裂症谱系障碍患者，以及 1059 名未受影响的兄弟姐妹和 586 名无关对照者，他们在基线时符合条件。在基线时收集基因型数据，而临床和社会人口统计学数据则在基线、三年和六年时收集。基于群组的轨迹建模应用于一般认知的加权标准化综合评分，以揭示认知亚型并探索随时间的轨迹。我们遵循标准程序计算多基因风险评分。使用随机效应序数回归模型研究 PRS 与认知亚型之间的关联。在患者、兄弟姐妹和对照组中发现了具有可变轨迹的五个认知亚型，在所有组合样本中发现了六个。PRS 显著预测了患者、兄弟姐妹和所有样本中较差的认知轨迹。经过 Bonferroni 校正和非遗传因素调整后，只有在所有组合样本中的结果仍然显著。精神分裂症的认知障碍具有异质性，可能与高 PRS 有关。我们的发现至少在所有组合样本中证实了精神分裂症和认知功能之间存在遗传重叠，并可以深入了解认知缺陷的机制。
