Alzheimer’s Genetics in the GWAS Era: A Continuing Story of ‘Replications and Refutations’
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After a decade of intensive investigation but only few replicable results, Alzheimer’s disease (AD) genetics research is slowly picking up pace. This is mostly owing to the completion of several genome-wide association studies (GWAS), which have suggested the existence of over three dozen potential new AD susceptibility genes. Although only a handful of these could be confirmed in subsequent independent replication efforts to date, this success rate is still much higher than in the pre-GWAS era. This review provides a brief summary of the principal methodologic advances in genetics research of the past decade, followed by a description of the most compelling findings that these advances have unearthed in AD. The paper closes with a discussion of the persistent methodologic difficulties and challenges and an outlook on what we can expect to gain from the next 10 years of AD genetics research.
KeywordsAlzheimer’s disease Causal genes Risk genes Susceptibility factors Genome-wide association study Meta-analysis Complex genetics
This work was sponsored by funding from the Cure Alzheimer Fund, the Michael J. Fox Foundation for Parkinson’s Research, and the German Federal Ministry for Education and Research (BMBF). L. Bertram was financially supported by funds from the Deutsche Forschungsgemeinschaft (DFG).
No potential conflict of interest relevant to this article was reported.
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