Benefits and Challenges of Rare Genetic Variation in Alzheimer’s Disease

摘要: It is well established that sporadic Alzheimer’s disease (AD) polygenic with common and rare genetic variation alongside environmental factors contributing to disease. Here, we review our current understanding of the architecture disease, paying specific attention susceptibility variants, explore some limitations in variant detection analysis. Rare has been shown robustly associate These include potentially damaging loss function mutations are easily modelled silico, vitro vivo, represent druggable targets. A number risk genes, including TREM2, SORL1 ABCA7 show multiple independent associations suggesting they may influence via mechanisms. With transcriptional regulation, inflammatory response modification protein production suggested be primary importance. We at beginning journey AD. Whole exome sequencing predominant technology choice. While fruitful, this introduced a challenges regard data integration. Ultimately future disease-associated identification lies whole genome projects will allow testing full range genomic variation.