基于人口的精神疾病风险与反复复发的拷贝数变异相关
Morteza Vaez1,2, Simone Montalbano1,2, Xabier Calle Sánchez1,2
1Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Roskilde, Denmark.
JAMA psychiatry
|June 26, 2024
概括
复发副本数变异 (rCNVs) 比以前认为的更常见,并具有较低的精神疾病风险. 基于人口的研究对于准确的遗传风险预测至关重要,与有偏见的病例控制研究不同.
科学领域:
- 遗传学 是一个遗传学.
- 精神病学是一个精神病学.
- 人口健康 人口健康
背景情况:
- 复发复制数变异 (rCNVs) 与病例控制研究中的精神疾病风险有关.
- 人口层面的rCNVs影响和流行程度在很大程度上是未知的.
研究的目的:
- 确定基于人口的无偏见的rCNVs在精神疾病中的患病率和风险估计.
- 为了比较不同精神病结局,rCNV剂量类型 (删除/重复) 和位置特征的风险.
主要方法:
- 在丹麦对iPSYCH病例-队列样本 (出生于1981-2008年,追踪到2015年) 的分析.
- 从新生儿血液样本中对27个自体rCNV位点进行基因定型.
- 权重考克斯比例危险和概括估计方程模型用于风险估计和比较.
主要成果:
- 在120267个人中确定了3547个rCNV; 流行率估计高于之前报告的.
- 大多数rCNV显示ADHD,ASD和SSD的风险增加适度,这些疾病的风险估计高度相关.
- 普拉德-威利/安吉尔曼综合征重复显示出高ASD风险 (HR 20.8);没有与MDD相关的rCNV;风险与位点大小和基因约束相关,而不是剂量类型.
结论:
- 几种rCNV比以前估计的更为普遍,并使精神疾病风险低.
- 案例控制研究可能会因为选择偏差而高估rCNV风险.
- 基于人口的风险估计对于临床应用中准确的遗传预测至关重要.
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