Andrews Shea J, Fulton-Howard Brian, Goate Alison
Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Equal first author.
Curr Genet Med Rep. 2019 Mar;7(1):1-12. doi: 10.1007/s40142-019-0156-2. Epub 2019 Jan 24.
Over the last decade over 40 loci have been associated with risk of Alzheimer's disease (AD). However, most studies have either focused on identifying risk loci or performing unbiased screens without a focus on protective variation in AD. Here, we provide a review of known protective variants in AD and their putative mechanisms of action. Additionally, we recommend strategies for finding new protective variants.
Recent Genome-Wide Association Studies have identified both common and rare protective variants associated with AD. These include variants in or near , , and .
There are very few protective variants with functional evidence and a derived allele with a frequency below 20%. Additional fine mapping and multi-omic studies are needed to further validate and characterize known variants as well as specialized genome-wide scans to identify novel variants.
在过去十年中，超过40个基因座与阿尔茨海默病（AD）风险相关。然而，大多数研究要么专注于识别风险基因座，要么进行无偏筛选，而没有关注AD中的保护性变异。在此，我们对AD中已知的保护性变异及其假定作用机制进行综述。此外，我们推荐寻找新的保护性变异的策略。
最近的全基因组关联研究已经鉴定出与AD相关的常见和罕见保护性变异。这些包括位于 、 及 内或附近的变异。
具有功能证据且衍生等位基因频率低于20%的保护性变异非常少。需要进一步的精细定位和多组学研究来进一步验证和表征已知变异，以及进行专门的全基因组扫描以识别新变异。
