Schizophrenia is a complex and chronic neuropsychiatric disorder, with a heritability of around 60-80%. Large (>100 kb) rare (<1%) copy number variants (CNVs) occur more frequently in schizophrenia patients compared to controls. Currently, there are no studies reporting genome-wide CNVs in clinical high risk for psychosis (CHR-P) individuals. The aim of this study was to investigate the role of rare genome-wide CNVs in 84 CHR-P individuals and 124 presumably healthy controls. There were no significant differences in all rare CNV frequencies and sizes between CHR-P individuals and controls. However, brain-related CNVs and brain-related deletions were significantly more frequent in CHR-P individuals than controls. In CHR-P individuals, significant associations were found between brain-related CNV carriers and attenuated positive symptoms syndrome or cognitive disturbances (OR = 3.07, p = .0286). Brain-related CNV carriers experienced significantly higher negative symptoms (p = .0047), higher depressive symptoms (p = .0175), and higher disturbances of self and surroundings (p = .0029) than noncarriers. Furthermore, enrichment analysis of genes was performed in the regions of rare CNVs using three independent methods, which confirmed significant clustering of predefined genes involved in synaptic/brain-related functional pathways in CHR-P individuals. These results suggest that rare CNVs might affect synaptic/brain-related functional pathways in CHR-P individuals.

中文翻译：

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临床上有精神病高风险的个体中的罕见拷贝数变异：突触/大脑相关功能途径的丰富。

精神分裂症是一种复杂的慢性神经精神疾病，遗传力约为60-80％。与对照相比，精神分裂症患者中较大（> 100 kb）罕见（<1％）拷贝数变异（CNV）的发生率更高。当前，尚无研究报告全基因组CNV导致精神病（CHR-P）个人临床高风险。这项研究的目的是调查在84个CHR-P个体和124个可能健康的对照中罕见的全基因组CNV的作用。在CHR-P个人和对照组之间，所有罕见CNV频率和大小均无显着差异。然而，与对照组相比，CHR-P个体中与脑相关的CNV和与脑相关的缺失明显更为频繁。在CHR-P个人中，发现与脑相关的CNV携带者与减毒的阳性症状综合征或认知障碍之间存在显着相关性（OR = 3.07，p = .0286）。与非相关者相比，与脑相关的CNV携带者遭受的阴性症状（p = .0047），抑郁症状（p = .0175）和对自身和周围环境的干扰（p = .0029）明显更高。此外，使用三种独立的方法在稀有CNV区域进行了基因富集分析，这证实了参与CHR-P个体突触/脑相关功能途径的预定义基因的显着聚集。这些结果表明，罕见的CNV可能会影响CHR-P个体的突触/大脑相关功能途径。与非相关者相比，与脑相关的CNV携带者遭受的阴性症状（p = .0047），抑郁症状（p = .0175）和对自身和周围环境的干扰（p = .0029）明显更高。此外，使用三种独立的方法在稀有CNV区域进行了基因富集分析，这证实了参与CHR-P个体突触/脑相关功能途径的预定义基因的显着聚集。这些结果表明，罕见的CNV可能会影响CHR-P个体的突触/大脑相关功能途径。与非相关者相比，与脑相关的CNV携带者遭受的阴性症状（p = .0047），抑郁症状（p = .0175）和对自身和周围环境的干扰（p = .0029）明显更高。此外，使用三种独立的方法在稀有CNV区域进行了基因富集分析，这证实了参与CHR-P个体突触/脑相关功能途径的预定义基因的显着聚集。这些结果表明，罕见的CNV可能会影响CHR-P个体的突触/大脑相关功能途径。证实了CHR-P个体中涉及突触/脑相关功能途径的预定义基因的显着聚集。这些结果表明，罕见的CNV可能会影响CHR-P个体的突触/大脑相关功能途径。证实了CHR-P个体中涉及突触/脑相关功能途径的预定义基因的显着聚集。这些结果表明，罕见的CNV可能会影响CHR-P个体的突触/大脑相关功能途径。