Published in

Frontiers Media, Frontiers in Genetics, (5)

DOI: 10.3389/fgene.2014.00369



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Identification of rare variants in Alzheimer’s disease

Journal article published in 2014 by Jenny Lord ORCID, Alexander J. Lu, Carlos Cruchaga
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO


Much progress has been made in recent years in identifying genes involved in the risk of developing Alzheimer’s disease (AD), the most common form of dementia. Yet despite the identification of over 20 disease associated loci, mainly through genome wide association studies (GWAS), a large proportion of the genetic component of the disorder remains unexplained. Recent evidence from the AD field, as with other complex diseases, suggests a large proportion of this “missing heritability” may be due to rare variants of moderate to large effect size, but the methodologies to detect such variants are still in their infancy. The latest studies in the field have been focused on the identification of coding variation associated with AD risk, through whole-exome or whole-genome sequencing. Such variants are expected to have larger effect sizes than GWAS loci, and are easier to functionally characterize, and develop cellular and animal models for. This review explores the issues involved in detecting rare variant associations in the context of AD, highlighting some successful approaches utilized to date.