阿尔茨海默病的基因组学与功能基因组学研究进展

 阿尔茨海默病（AD）是最常见的神经退行性疾病与最主要的痴呆类型，其发病率随着年龄增加而呈指数式增长。随着人口老龄化，AD造成的社会经济负担愈趋严重。AD的遗传力接近80%，其人群易感程度、表型差异等性状特征受机体遗传变异的极大影响。总结了基于家系连锁分析、病例对照全基因组关联分析、全基因组测序等基因组学分析手段鉴定与AD发生发展相关的遗传变异与风险基因，梳理了基于各种组学数据的功能基因组学研究手段，解析遗传变异背后的调控元件、效应基因及其分子过程的研究进展。对风险基因及其转录与蛋白水平改变的揭示，可为AD的发病机制解析、药物开发、精准诊断与早期预测提供直接的靶点。

Genomics and functional genomics of Alzheimer's disease

The Alzheimer's disease (AD) is a major form of dementia and the most prevalent neurodegenerative disease in the elderly. In view of its high heritability, the genetic and genomic study plays essential roles in the basic researches and the clinical practice of the AD. This paper reviews the research advances regarding the genetic analyses of the AD, from the linkage analyses and the genome-wide association studies, to the next-generation sequencing studies, including also the functional variations, the causal genes, the multi-omic alterations, and the biological mechanisms underlying the AD genetics from the perspective of the functional genomics. It is expected that the genomic and functional genomic studies will contribute to the understanding and the management of the disease.