Background

Patients with sporadic Alzheimer’s do not possess an identified causative variant and hold an estimated heritability of 92–100%. Majority of disease causing, or protective mutations were uncommon in a generic group of the population, whereas dominant variants were well identified. Development of next-generation sequencing along with genome-wide association studies allowed to accurately identify the lesser-known disease-causing variants essential for the early detection of AD in sporadic patients to provide genetic counsel and prophylactic treatment.

Objective

The objective of the review is to bring the focus to the potentiality of large-scale GWAS (Genome-Wide Association Studies) analysis for the detection of novel genes for the sporadic Alzheimer’s disease.

Results

Identification of infrequently studied genes like LILRB2, LIPC, ITGAX, HLA-A, CASP8, ABCA7, ADAM10, BIN1, CD33, CLU, EPHA1, GAB2, PICALM, TREM2, SORL1, MAPT, HLA for the sporadic AD, that interact with predominant AD genes and engages in pathways mediating disease progression.

Conclusion

A multi-population large-scale un-targeted whole-genome GWAS or WES (whole exome sequencing) analysis is needed to identify several genes and variants besides the predominantly studied APOE for the sporadic case of Alzheimer’s.

中文翻译：

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GWAS在发现散发性阿尔茨海默氏病的非目标遗传关联中的重要性

背景

散发性阿尔茨海默氏病的患者没有确定的致病变异，估计遗传力为92–100％。在一般人群中，大多数致病或保护性突变并不常见，而显性变体得到了很好的识别。下一代测序技术的发展以及全基因组关联研究的发展，使得人们能够准确地识别出鲜为人知的致病变异，这些变异对于散发患者中的AD的早期发现至关重要，从而可以提供遗传咨询和预防性治疗。

客观的

审查的目的是将重点放在大规模GWAS（全基因组关联研究）分析的潜力上，以检测散发性阿尔茨海默氏病的新基因。

结果

识别与偶发性AD相互作用的，不经常研究的基因，例如LILRB2，LIPC，ITGAX，HLA-A，CASP8，ABCA7，ADAM10，BIN1，CD33，CLU，EPHA1，GAB2，PICALM，TREM2，SOLL1，MAPT，HLA AD基因并参与介导疾病进展的途径。

结论

除了主要研究针对偶发性阿尔茨海默氏病的APOE之外，还需要多人群大规模无目标全基因组GWAS或WES（全外显子组测序）分析，以鉴定几种基因和变异体。