Lee Brian N, Wang Junwen, Nho Kwangsik, Saykin Andrew J, Shen Li
University of Pennsylvania, Philadelphia, PA, USA.
Mayo Clinic, Phoenix, AZ, USA.
AMIA Jt Summits Transl Sci Proc. 2023 Jun 16;2023:340-349. eCollection 2023.
Alzheimer's Disease (AD) is a highly heritable neurodegenerative disorder characterized by memory impairments. Understanding how genetic factors contribute to AD pathology may inform interventions to slow or prevent the progression of AD. We performed stratified genetic analyses of 1,574 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants to examine associations between levels of quantitative traits (QT's) and future diagnosis. The Chow test was employed to determine if an individual's genetic profile affects identified predictive relationships between QT's and future diagnosis. Our chow test analysis discovered that cognitive and PET-based biomarkers differentially predicted future diagnosis when stratifying on allelic dosage of AD loci. Post-hoc bootstrapped and association analyses of biomarkers confirmed differential effects, emphasizing the necessity of stratified models to realize individualized AD diagnosis prediction. This novel application of the Chow test allows for the quantification and direct comparison of genetic-based differences. Our findings, as well as the identified QT-future diagnosis relationships, warrant future investigation from a biological context.
阿尔茨海默病（AD）是一种具有高度遗传性的神经退行性疾病，其特征为记忆障碍。了解遗传因素如何导致AD病理变化，可能为减缓或预防AD进展的干预措施提供依据。我们对1574名阿尔茨海默病神经影像学计划（ADNI）参与者进行了分层遗传分析，以研究数量性状（QT）水平与未来诊断之间的关联。采用Chow检验来确定个体的遗传概况是否会影响已确定的QT与未来诊断之间的预测关系。我们的Chow检验分析发现，在根据AD基因座的等位基因剂量进行分层时，认知和基于PET的生物标志物对未来诊断的预测存在差异。对生物标志物进行事后自抽样和关联分析证实了这些差异效应，强调了分层模型对于实现个性化AD诊断预测的必要性。Chow检验的这一新颖应用能够对基于遗传的差异进行量化和直接比较。我们的研究结果以及所确定的QT与未来诊断之间的关系，值得从生物学角度进行进一步研究。
