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Editorial
January 2015

Exploring the Epigenetics of Alzheimer Disease

Author Affiliations
  • 1Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland
  • 2Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, Maryland
JAMA Neurol. 2015;72(1):8-9. doi:10.1001/jamaneurol.2014.3057

Genome-wide association studies have been tremendously successful at unraveling the genetic architecture of neurological disorders (see http://www.genome.gov/gwastudies/ for an updated list). Alzheimer disease is a particularly good example of the power of this technology, with multiple loci already identified.1 Although the publication of a susceptibility locus is an important milestone in any disease, it represents only the opening act because the identity of the responsible gene within a locus is not always obvious. Without this knowledge, it becomes difficult (if not impossible) to establish a functional connection between genetic variation and the underlying pathobiology. Not surprisingly, this circumstance is a major challenge now faced by the entire genomics field. To bridge this gap, a multipronged approach has been adopted to delineate the effect of genetic variation on the expression of neighboring genes (known as expression quantitative trait loci mapping2) and to quantify the effects of epigenetic phenomena in regulating gene transcription. The term epigenetics covers a gamut of mechanisms such as DNA methylation, chromatin remodeling, gene expression regulation by microRNA, histone modification, and others.

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