阿尔茨海默病的遗传学：多基因和上位性成分的重要性
Genetics of Alzheimer's Disease: the Importance of Polygenic and Epistatic Components.
作者信息
Raghavan Neha, Tosto Giuseppe
机构信息
The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, 622 W. 168th Street PH 19-314, New York, NY, 10032, USA.
Department of Neurology, Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital, New York, NY, 10032, USA.
出版信息
Curr Neurol Neurosci Rep. 2017 Aug 21;17(10):78. doi: 10.1007/s11910-017-0787-1.
PURPOSE OF REVIEW
We aimed to summarize the recent advances in genetic findings of Alzheimer's disease (AD), focusing on traditional single-marker and gene approaches and non-traditional ones, i.e., polygenic and epistatic components.
RECENT FINDINGS
Genetic studies have progressed over the last few decades from linkage to genome-wide association studies (GWAS), and most recently studies utilizing high-throughput sequencing. So far, GWASs have identified several common variants characterized by small effect sizes (besides APOE-ε4). Sequencing has facilitated the study of rare variants with larger effects. Nevertheless, missing heritability for AD remains extensive; a possible explanation might lie in the existence of polygenic and epistatic components. We review findings achieved by single-marker approaches, but also polygenic and epistatic associations. The latter two are critical, yet-underexplored mechanisms. Genes involved in complex diseases are likely regulated by mechanisms and pathways involving many other genes, an aspect potentially missed by traditional approaches.
综述目的
我们旨在总结阿尔茨海默病（AD）基因研究的最新进展，重点关注传统的单标记和基因方法以及非传统方法，即多基因和上位性成分。
最新发现
在过去几十年中，基因研究已从连锁分析发展到全基因组关联研究（GWAS），最近又发展到利用高通量测序的研究。到目前为止，GWAS已经鉴定出几个效应量较小的常见变异（除了APOE-ε4）。测序有助于对效应较大的罕见变异进行研究。然而，AD的遗传力缺失仍然广泛存在；一个可能的解释可能在于多基因和上位性成分的存在。我们回顾了通过单标记方法以及多基因和上位性关联所取得的发现。后两者是关键但尚未充分探索的机制。复杂疾病相关基因可能受涉及许多其他基因的机制和途径调控，而这是传统方法可能遗漏的一个方面。
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