Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, 3584 CG Utrecht, The Netherlands.
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
Genes (Basel). 2022 Apr 14;13(4):695. doi: 10.3390/genes13040695.
Schizophrenia and bipolar disorder are neurodevelopmental disorders with overlapping symptoms and a shared genetic background. Deviations in intracranial volume (ICV)—a marker for neurodevelopment—differ between schizophrenia and bipolar disorder. Here, we investigated whether genetic risk for schizophrenia and bipolar disorder is related to ICV in the general population by using the UK Biobank data (n = 20,196). Polygenic risk scores for schizophrenia (SZ-PRS) and bipolar disorder (BD-PRS) were computed for 12 genome wide association study P-value thresholds (PT) for each individual and correlations with ICV were investigated. Partial correlations were performed at each PT to investigate whether disease specific genetic risk variants for schizophrenia and bipolar disorder show different relationships with ICV. ICV showed a negative correlation with SZ-PRS at PT ≥ 0.005 (r < −0.02, p < 0.005). ICV was not associated with BD-PRS; however, a positive correlation between BD-PRS and ICV at PT = 0.2 and PT = 0.4 (r = +0.02, p < 0.005) appeared when the genetic overlap between schizophrenia and bipolar disorder was accounted for. Despite small effect sizes, a higher load of schizophrenia risk genes is associated with a smaller ICV in the general population, while risk genes specific for bipolar disorder are correlated with a larger ICV. These findings suggest that schizophrenia and bipolar disorder risk genes, when accounting for the genetic overlap between both disorders, have opposite effects on early brain development.
精神分裂症和双相情感障碍是具有重叠症状和共同遗传背景的神经发育障碍。脑容量（ICV）——神经发育的标志物——在精神分裂症和双相情感障碍之间存在差异。在这里，我们通过使用英国生物银行（UK Biobank）的数据（n=20196）研究了精神分裂症和双相情感障碍的遗传风险是否与普通人群的 ICV 相关。为每个个体计算了精神分裂症（SZ-PRS）和双相情感障碍（BD-PRS）的多基因风险评分（PRS），并研究了与 ICV 的相关性。在每个 PT 进行部分相关分析，以研究精神分裂症和双相情感障碍的特定疾病遗传风险变异是否与 ICV 存在不同的关系。当考虑到精神分裂症和双相情感障碍之间的遗传重叠时，ICV 与 SZ-PRS 在 PT≥0.005 时呈负相关（r<−0.02，p<0.005）。ICV 与 BD-PRS 无关；然而，当考虑到精神分裂症和双相情感障碍之间的遗传重叠时，在 PT=0.2 和 PT=0.4 时，BD-PRS 与 ICV 之间出现正相关（r=+0.02，p<0.005）。尽管效应大小较小，但一般人群中精神分裂症风险基因的负荷越高，ICV 越小，而双相情感障碍特有的风险基因与较大的 ICV 相关。这些发现表明，当考虑到两种疾病之间的遗传重叠时，精神分裂症和双相情感障碍的风险基因对早期大脑发育有相反的影响。
