Polygenic Risk Scores Differentiating Schizophrenia From Bipolar Disorder Are Associated With Premorbid Intelligence in Schizophrenia Patients and Healthy Subjects.
Polygenic Risk Scores Differentiating Schizophrenia From Bipolar Disorder Are Associated With Premorbid Intelligence in Schizophrenia Patients and Healthy Subjects.
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DOI：
10.1093/ijnp/pyab014
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发表时间：
2021-07-23
期刊：
影响因子：
--
通讯作者：
Shioiri T
中科院分区：
文献类型：
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作者：
Ohi K;Nishizawa D;Sugiyama S;Takai K;Kuramitsu A;Hasegawa J;Soda M;Kitaichi K;Hashimoto R;Ikeda K;Shioiri T
精神分裂症（SCZ）患者的智力损伤比双相情感障碍（BD）患者更严重，尽管两种疾病的临床和遗传相似。已经确定了区分SCZ和BD的遗传位点，即SCZ特异性风险。SCZ患者的多基因[风险]评分（pgs）高于健康对照组（hc）。然而，遗传风险对智力受损的影响尚不清楚。在这里，我们研究了SCZ特异性风险是否可以预测SCZ患者和hc的智力损伤。利用SCZ与BD、儿童智力（CHI）和成年智力相关的大规模全基因组关联研究数据集（n = 12 441-282 014）计算pgs。计算了130例SCZ患者和146例hcc患者的全基因组关联研究的pgs。测量SCZ患者和hc患者的发病前和当前智力水平及其下降情况。研究了pgs与智力功能之间的相关性。SCZ特异性风险的高pgs与SCZ患者和hc的低发病前智力相关（β = - 0.17, P = 4.12 × 10-3）。在调整诊断状态后，相关性仍然显著（β = - 0.13, P = 0.024）。scz特异性风险的pgs与当前智力或智力下降无显著相关性（P < 0.05）。SCZ患者CHI的pgs低于hcc患者（R2 = 0.025, P = 0.05）。025)，而CHI的pgs与发病前和当前智力、智力下降或scz特异性风险的pgs无显著相关性（P < 0.05）。这些结果提示，区分SCZ与BD的遗传因素可能通过病前智力（即结晶智力）的损害影响SCZ的发病机制和/或SCZ与BD的病理差异，而CHI的遗传因素可能影响SCZ的发病机制，但不通过智力损害影响。
Impairments in intelligence are more severe in patients with schizophrenia (SCZ) than in patients with bipolar disorder (BD) despite clinical and genetic similarities between the disorders. Genetic loci differentiating SCZ from BD, that is, SCZ-specific risk, have been identified. Polygenetic [risk] scores (PGSs) for SCZ-specific risk are higher in SCZ patients than in healthy controls (HCs). However, the influence of genetic risk on impaired intelligence is poorly understood. Here, we investigated whether SCZ-specific risk could predict impairments in intelligence in SCZ patients and HCs. Large-scale genome-wide association study datasets related to SCZ vs BD, childhood intelligence (CHI), and adulthood intelligence (n = 12 441–282 014) were utilized to compute PGSs. PGSs derived from the genome-wide association studies were calculated for 130 patients with SCZ and 146 HCs. Premorbid and current intelligence and the decline were measured in SCZ patients and HCs. Correlations between PGSs and intelligence functions were investigated. High PGSs for SCZ-specific risk were correlated with low premorbid intelligence in SCZ patients and HCs (β = −0.17, P = 4.12 × 10–3). The correlation was still significant after adjusting for diagnostic status (β = −0.13, P = .024). There were no significant correlations between PGSs for SCZ-specific risk and current intelligence or intelligence decline (P > .05). PGSs for CHI were lower in SCZ patients than in HCs (R2 = 0.025, P = .025), while the PGSs for CHI were not significantly correlated with premorbid and current intelligence, the decline, or the PGSs for SCZ-specific risk (P > .05). These findings suggest that genetic factors differentiating SCZ from BD might affect the pathogenesis of SCZ and/or pathological differences between SCZ and BD via the impairment of premorbid intelligence, that is, crystallized intelligence, while genetic factors for CHI might affect the pathogenesis of SCZ but not via impairments in intelligence.
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