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Genetics of Alzheimer’s Disease: the Importance of Polygenic and Epistatic Components

  • Dementia (K S Marder, Section Editor)
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Abstract

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.

Summary

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.

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Acknowledgements

Dr. Tosto is supported by NIH grant R21AG054832

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Authors and Affiliations

  1. The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, 622 W. 168th Street PH 19-314, New York, NY, 10032, USA

    Neha Raghavan & Giuseppe Tosto

  2. Department of Neurology, Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital, New York, NY, 10032, USA

    Neha Raghavan & Giuseppe Tosto

  3. Institute for Genomic Medicine, Columbia University, New York, NY, 10032, USA

    Neha Raghavan

  4. The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, 622 W. 168th Street PH 19-314, New York, NY, 10032, USA

    Giuseppe Tosto

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  1. Neha Raghavan
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  2. Giuseppe Tosto
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Correspondence to Giuseppe Tosto.

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Neha Raghavan and Giuseppe Tosto each declare no potential conflicts of interest.

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This article is part of the Topical Collection on Dementia

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Raghavan, N., Tosto, G. Genetics of Alzheimer’s Disease: the Importance of Polygenic and Epistatic Components. Curr Neurol Neurosci Rep 17, 78 (2017). https://doi.org/10.1007/s11910-017-0787-1

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