Genomic variants, genes, and pathways of Alzheimer's disease: An overview.

TitleGenomic variants, genes, and pathways of Alzheimer's disease: An overview.
Publication TypeJournal Article
Year of Publication2017
AuthorsNaj AC, Schellenberg GD
Corporate AuthorsAlzheimer's Disease Genetics Consortium(ADGC)
JournalAm J Med Genet B Neuropsychiatr Genet
Date Published2017 01
KeywordsAlzheimer Disease, Dementia, Genetic Linkage, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genomics, Humans, Polymorphism, Single Nucleotide

Alzheimer's disease (AD) (MIM: 104300) is a highly heritable disease with great complexity in its genetic contributors, and represents the most common form of dementia. With the gradual aging of the world's population, leading to increased prevalence of AD, and the substantial cost of care for those afflicted, identifying the genetic causes of disease represents a critical effort in identifying therapeutic targets. Here we provide a comprehensive review of genomic studies of AD, from the earliest linkage studies identifying monogenic contributors to early-onset forms of AD to the genome-wide and rare variant association studies of recent years that are being used to characterize the mosaic of genetic contributors to late-onset AD (LOAD), and which have identified approximately ∼20 genes with common variants contributing to LOAD risk. In addition, we explore studies employing alternative approaches to identify genetic contributors to AD, including studies of AD-related phenotypes and multi-variant association studies such as pathway analyses. Finally, we introduce studies of next-generation sequencing, which have recently helped identify multiple low-frequency and rare variant contributors to AD, and discuss on-going efforts with next-generation sequencing studies to develop statistically well- powered and comprehensive genomic studies of AD. Through this review, we help uncover the many insights the genetics of AD have provided into the pathways and pathophysiology of AD. © 2016 Wiley Periodicals, Inc.

Alternate JournalAm. J. Med. Genet. B Neuropsychiatr. Genet.
PubMed ID27943641
PubMed Central IDPMC6179157
Grant ListU01 AG032984 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States