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Abstract：
OBJECTIVE: The present study aimed to examine the association between copy number variations (CNVs) in parkin (PRKN) and schizophrenia (SCZ) and autism spectrum disorder (ASD) in a large case-control sample.
METHODS: Array comparative genomic hybridization was performed on 3111 cases with SCZ, 1236 cases with ASD, and 2713 controls. We systematically prioritized likely pathogenic CNVs (LP-CNVs) in PRKN and examined their association with SCZ and ASD.
RESULTS: In total, 3014 SCZ cases (96.9%), 1205 ASD cases (97.5%), and 2671 controls (98.5%) passed quality control. We found that monoallelic carriers of LP-CNVs in PRKN were common (70/6890, 1.02%) and were not at higher risk of SCZ (p = 0.29) or ASD (p = 0.72). We observed that the distribution pattern of LP-CNVs in the Japanese population was consistent with those in other populations. We also identified a patient diagnosed with SCZ and early-onset Parkinson\'s disease carrying biallelic pathogenic CNVs in PRKN. The absence of Parkinson\'s symptoms in 10 other monoallelic carriers of the same pathogenic CNV further reflects the lack of effect of monoallelic pathogenic variants in PRKN in the absence of a second hit.
CONCLUSIONS: The present findings suggest that monoallelic CNVs in PRKN do not confer a significant risk for SCZ or ASD. However, further studies to investigate the association between biallelic CNVs in PRKN and SCZ and ASD are warranted.
METHODS: Array comparative genomic hybridization was performed on 3111 cases with SCZ, 1236 cases with ASD, and 2713 controls. We systematically prioritized likely pathogenic CNVs (LP-CNVs) in PRKN and examined their association with SCZ and ASD.
RESULTS: In total, 3014 SCZ cases (96.9%), 1205 ASD cases (97.5%), and 2671 controls (98.5%) passed quality control. We found that monoallelic carriers of LP-CNVs in PRKN were common (70/6890, 1.02%) and were not at higher risk of SCZ (p = 0.29) or ASD (p = 0.72). We observed that the distribution pattern of LP-CNVs in the Japanese population was consistent with those in other populations. We also identified a patient diagnosed with SCZ and early-onset Parkinson\'s disease carrying biallelic pathogenic CNVs in PRKN. The absence of Parkinson\'s symptoms in 10 other monoallelic carriers of the same pathogenic CNV further reflects the lack of effect of monoallelic pathogenic variants in PRKN in the absence of a second hit.
CONCLUSIONS: The present findings suggest that monoallelic CNVs in PRKN do not confer a significant risk for SCZ or ASD. However, further studies to investigate the association between biallelic CNVs in PRKN and SCZ and ASD are warranted.
摘要：
目的：本研究旨在研究大病例对照样本中帕金（PRKN）与精神分裂症（SCZ）和自闭症谱系障碍（ASD）的拷贝数变异（CNV）之间的关联。
方法：对3111例SCZ，1236例ASD，和2713个控件。我们系统地优先考虑PRKN中可能的致病性CNVs（LP-CNVs），并检查它们与SCZ和ASD的关联。
结果：总计，3014例SCZ（96.9%），1205例ASD（97.5%），2671名对照(98.5%)通过质量控制。我们发现，PRKN中LP-CNV的单等位基因携带者是常见的（70/6890，1.02%），并且没有较高的SCZ（p=0.29）或ASD（p=0.72）风险。我们观察到LP-CNV在日本人群中的分布模式与其他人群一致。我们还确定了一名诊断为SCZ和早发性帕金森病的患者，在PRKN中携带双等位基因致病性CNV。在10个相同致病性CNV的其他单等位基因携带者中没有帕金森氏症症状进一步反映了在没有第二次打击的情况下PRKN中单等位基因致病性变体的缺乏作用。
结论：目前的研究结果表明，PRKN中的单等位基因CNVs不会赋予SCZ或ASD的显著风险。然而,有必要进一步研究PRKN中的双等位基因CNVs与SCZ和ASD之间的关联.
方法：对3111例SCZ，1236例ASD，和2713个控件。我们系统地优先考虑PRKN中可能的致病性CNVs（LP-CNVs），并检查它们与SCZ和ASD的关联。
结果：总计，3014例SCZ（96.9%），1205例ASD（97.5%），2671名对照(98.5%)通过质量控制。我们发现，PRKN中LP-CNV的单等位基因携带者是常见的（70/6890，1.02%），并且没有较高的SCZ（p=0.29）或ASD（p=0.72）风险。我们观察到LP-CNV在日本人群中的分布模式与其他人群一致。我们还确定了一名诊断为SCZ和早发性帕金森病的患者，在PRKN中携带双等位基因致病性CNV。在10个相同致病性CNV的其他单等位基因携带者中没有帕金森氏症症状进一步反映了在没有第二次打击的情况下PRKN中单等位基因致病性变体的缺乏作用。
结论：目前的研究结果表明，PRKN中的单等位基因CNVs不会赋予SCZ或ASD的显著风险。然而,有必要进一步研究PRKN中的双等位基因CNVs与SCZ和ASD之间的关联.
