Importance of GWAS in finding un-targeted genetic association of sporadic Alzheimer's disease

초록

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. © 2021, The Korean Society of Toxicogenomics and Toxicoproteomics.

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