Raghavan H, et al. -- The authors aimed to summarize recent advances in genetic findings for Alzheimer's disease (AD). They focused on traditional single–marker and gene approaches and non–traditional ones, for example, polygenic and epistatic components. They found that 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.

Findings:

• GWASs have identified several common variants characterized by small effect sizes (besides APOE–eplsilon 4).
• Sequencing has facilitated the study of rare variants with larger effects.
• Missing heritability for AD remains extensive; a possible explanation might lie in the existence of polygenic and epistatic components.

Summary

• Researchers review the 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 to be regulated by mechanisms and pathways involving many other genes, an aspect potentially missed by traditional approaches.