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.
Keywords: Epistasis; GWAS; Next-generation sequencing; Polygenic risk score.