在强迫症障碍中的罕见副本数变体的负担
Matthew Halvorsen1, Elles de Schipper, Julia Boberg
1University of North Carolina at Chapel Hill.
Research square
|January 23, 2024
概括
大量,罕见的副本数变异 (CNVs) 导致强迫症 (OCD) 风险,特别是不耐受基因的缺失. 这些遗传变异也与伴随性自闭症和强迫症患者治疗反应的减少相关.
科学领域:
- 遗传学 遗传学 是一个
- 神经科学是一个神经科学.
- 精神病学是一个精神病学.
背景情况:
- 之前关于强迫症 (OCD) 的遗传研究已经确定了常见单核酸变体 (SNV),罕见编码SNV和小插入删除 (indels) 的贡献.
- 大,罕见的副本数变异 (CNVs) 在强迫症风险中的作用尚未在规模上进行广泛研究.
研究的目的:
- 评估大型,罕见的CNVs对发展强迫症的风险的贡献.
- 调查强迫症中CNV和临床表型之间的关联,包括并发症和治疗反应.
主要方法:
- 从基因型阵列数据对2,248例强迫症病例和3,608名瑞典和挪威不受影响的对照群的罕见CNV的分析.
- 评估CNV负担,重点关注重叠的蛋白质编码区域和功能丧失不耐受基因 (pLI>0.995).
- 在1,612个病例的子集中,对CNV携带者和临床数据的相关性分析,包括自闭症并发症和治疗反应.
主要成果:
- 与对照组相比,强迫症病例的CNV重量 (>30kb) 增加了 (OR=1.12,P=1.77×10-3).
- 对于CNV重叠蛋白质编码区域 (OR=1.19,P=3.08×10-4),特别是高度不耐受基因的缺失 (pLI>0.995,OR=4.12,P=2.54×10-5),这种关联更强烈.
- 神经发育重复的携带者更有可能患上并发性自闭症 (P<0.001),删除携带者表现出较低的治疗反应 (P=0.02).
结论:
- 大型,罕见的CNVs代表了强迫症的显著遗传风险因素.
- CNV重叠的神经发育基因与特定的临床特征有关,包括自闭症并发症和治疗效率降低.
- 纳入罕见的CNV分析可以增强遗传研究的力量,以确定强迫症风险基因.
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