基于深度学习的多基因分数增强了精神疾病的概括性预测
Leonardo Cobuccio1,2,3, Arnor I Sigurdsson1, Kajsa-Lotta Georgii Hellberg2
1Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
medRxiv : the preprint server for health sciences
|May 19, 2025
概括
深度学习 (DL) 模型显示,与线性模型相比,对预测诸如ADHD,ASD和MDD等精神疾病的概括性有所改善. 然而,线性模型对于遗传风险预测仍然有效,特别是当将多基因得分 (PGS) 和家族遗传风险得分 (FGRS) 结合起来时.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 精神病学流行病学 精神病学流行病学
- 计算生物学 计算生物学
背景情况:
- 多基因分数 (PGS) 越来越多地用于从遗传数据中预测复杂的特征.
- 对精神疾病的PGS的预测性能有限,并且对线性模型的深度学习 (DL) 的实用性尚不清楚.
- 研究的精神疾病包括注意力缺陷/多动障碍 (ADHD),自闭症谱系障碍 (ASD),双极性障碍 (BIP),严重抑郁障碍 (MDD) 和精神分裂症 (SCZ).
研究的目的:
- 为了比较新的DL模型,基因组局部网络 (GLN) 的预测性能,与使用个人级别基因型数据的五种精神疾病的线性模型 (bigstatsr) 进行比较.
- 评估将内部 (基于个体的) PGS与外部 (GWAS衍生的) PGS和家庭遗传风险评分 (FGRSs) 结合起来,以预测的附加值.
- 评估DL是否在整合不同类型的遗传风险信息方面比物流模型提供优势.
主要方法:
- 用GLN (DL) 和bigstatsr (线性模型) 对5种精神疾病的样本内和样本外预测进行比较.
- 评估结合内部PGS,外部PGS和FGRS的添加和协同效应.
- 基于DL的整合与综合遗传风险得分的物流模型的评估.
主要成果:
- GLN和bigstatsr在样本中的表现相似.
- GLN显示了ADHD,ASD和MDD的优异样本外概括,接收器操作特征曲线 (AUROC) 下的平均面积增长为0.026.
- 整合内部,外部和基于家庭的分数显著改善了ADHD预测,但DL整合并不总是超过后勤模型.
结论:
- 像GLN这样的深度学习模型可能会提高特定精神病特征的遗传风险预测的概括性.
- 线性模型在遗传风险预测方面仍然具有竞争力和有效性,特别是在整合多个遗传信息来源时.
- 需要进一步的研究才能充分利用DL来预测复杂的精神疾病.
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