导出基于孟德尔随机化的脑成像表型和双极性障碍的因果网络
Shane O'Connell1, Brielin C Brown2, Dara M Cannon3
1Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., New York, NY, 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., New York, NY, 10029, USA; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., New York, NY, 10029, USA.
概括
神经解剖学变异,特别是在白质区域,可能会导致双相情感障碍 (BD). 这项门德尔随机化研究表明,大脑结构影响了BD发育,为该疾病提供了新的见解.
科学领域:
- 神经科学是一个神经科学.
- 精神病学是一个精神病学.
- 遗传学 遗传学 是一个
背景情况:
- 之前的研究观察到双相情感障碍 (BD) 中的神经解剖学变异.
- 这些变化和BD之间的因果关系仍然不清楚.
研究的目的:
- 调查神经影像表现型和双相情感障碍 (BD) 之间的因果关系.
- 探索神经解剖学变异是否导致或是由BD引起的.
主要方法:
- 孟德尔随机化 (MR) 应用于英国生物银行神经成像数据和BD GWAS总结统计数据.
- 一个新的反向稀疏回归模型估计了直接因果效应 (DCE).
- 使用DCE权重得出因果分数,并应用于临床队列.
主要成果:
- 确定了28种显著的因果关系,其中27种显示神经成像影响BD的表型.
- 白质管道的表型显示,对BD的因果作用比反过来更强.
- 神经成像衍生的因果评分预测了青少年队列中的BD.
结论:
- 门德尔的随机化表明神经解剖学变异,特别是白质道,是BD的可能原因.
- 这些发现凸显了大脑结构在BD病因学中的潜在因果作用.
- 建议使用复制和三角化进行进一步的研究.
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