冲动性表型的纵向表征增强了基因组相关性和遗传性的信号
Wei Q Deng1,2, Kyla Belisario3,4, Marcus R Munafò5,6
1Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada. dengwq@mcmaster.ca.
Molecular psychiatry
|August 24, 2024
概括
这项研究揭示了冲动性特征的稳定遗传联系,例如随着时间推移延迟折扣. 纵向分析增强了遗传性估计,并验证了冲动性和相关精神疾病的多基因风险得分.
科学领域:
- 行为遗传学 行为遗传学
- 精神病学基因组学 精神病学基因学
- 发展心理学 发展心理学
背景情况:
- 全基因组关联研究 (GWAS) 使用横截面数据确定了与冲动性的遗传联系.
- 很少有研究使用纵向表型探索冲动性的分子遗传基础.
研究的目的:
- 通过使用纵向构建的特征,研究冲动性表型的分子遗传相关性.
- 评估纵向冲动性特征的遗传性和遗传相关性.
- 评估多基因风险评分 (PRSs) 与纵向冲动性和相关精神疾病的关联.
主要方法:
- 延迟折扣和UPPS-P冲动行为尺度的纵向表型是从3860名年龄在24岁,26岁和28岁的欧洲参与者中构建的,这些参与者是艾文长度研究的父母和孩子 (ALSPAC).
- 全基因组关联研究 (GWAS) 对横截面和纵向冲动性表型进行了研究.
- 估计了遗传性,表型和遗传相关性,并评估了与PRS的关联.
主要成果:
- 潜增长曲线建模表明,所有冲动性现象类型的时间间稳定拦截.
- 对于纵向延迟折扣 (0.22) 和感觉寻找 (0.35) 发现了显著的SNP遗传性.
- GWAS确定了与CADM2和NCAM1基因的关联,以及冲动性指标和自我调节障碍的PRS与纵向冲动性特征有显著的关联.
结论:
- 这项研究提供了冲动性特征的第一个纵向遗传分析,揭示了随着时间的推移稳定的基因组相关性.
- 纵向的表型,特别是潜伏的拦截,可以增强遗传性估计和基因组关联信号.
- 研究结果支持PRS在理解冲动性及其与精神疾病的联系方面具有实用性.
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