Dementia Research Institute, Cardiff University, UK.
Dementia Research Institute, Cardiff University, UK.
Neurobiol Dis. 2020 Aug;142:104953. doi: 10.1016/j.nbd.2020.104953. Epub 2020 May 20.
In this paper we explore the phenomenon of pleiotropy in neurodegenerative diseases, focusing on Alzheimer's disease (AD). We summarize the various techniques developed to investigate pleiotropy among traits, elaborating in the polygenic risk scores (PRS) analysis. PRS was designed to assess a cumulative effect of a large number of SNPs for association with a disease and, later for disease risk prediction. Since genetic predictions rely on heritability, we discuss SNP-based heritability from genome-wide association studies and its contribution to the prediction accuracy of PRS. We review work examining pleiotropy in neurodegenerative diseases and related phenotypes and biomarkers. We conclude that the exploitation of pleiotropy may aid in the identification of novel genes and provide further insights in the disease mechanisms, and along with PRS analysis, may be advantageous for precision medicine.
在本文中，我们探讨了神经退行性疾病中多效性的现象，重点关注阿尔茨海默病（AD）。我们总结了各种用于研究特征之间多效性的技术，详细阐述了多基因风险评分（PRS）分析。PRS 旨在评估大量 SNP 与疾病的关联的累积效应，并随后用于疾病风险预测。由于遗传预测依赖于遗传度，我们讨论了基于 SNP 的遗传度来自全基因组关联研究及其对 PRS 预测准确性的贡献。我们综述了检查神经退行性疾病和相关表型及生物标志物中多效性的工作。我们的结论是，利用多效性可以帮助鉴定新的基因，并为疾病机制提供更深入的见解，并且与 PRS 分析相结合，可能有利于精准医学。
