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Alzheimer's disease risk genes and the age-at-onset phenotype.

TitleAlzheimer's disease risk genes and the age-at-onset phenotype.
Publication TypeJournal Article
Year of Publication2013
AuthorsThambisetty, M, An, Y, Tanaka, T
JournalNeurobiol Aging
Date Published2013 Nov
KeywordsAdult, Age of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoprotein E4, Cohort Studies, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Linear Models, Male, Middle Aged, Monomeric Clathrin Assembly Proteins, Phenotype, Polymorphism, Genetic, Risk Factors

Despite the recent identification of several novel risk genes for Alzheimer's disease (AD), little is known about their influence on the age at onset (AAO) of AD. The AAO is a phenotype with a heritable component distinct from disease risk and may be a useful trait to study in the context of developing interventions for delaying the onset of AD. We studied the influence of 10 recently identified AD risk genes and APOE in relation to AAO in a large cohort of AD patients (N = 2569). We find that the novel AD risk gene, PICALM, exerts a small effect on the AAO of AD with earlier disease onset in risk allele carriers. In addition, we confirmed the previously reported association between the APOE ε4 allele and earlier disease onset. None of the other AD risk genes influenced AAO of AD. Our results suggest that besides APOE, other genes associated with AD risk do not exert large effects on the AAO phenotype of AD.

Alternate JournalNeurobiol. Aging
PubMed ID23870418
PubMed Central IDPMC4038407
Grant ListU01 AG016976 / AG / NIA NIH HHS / United States
Z99 AG999999 / / Intramural NIH HHS / United States
U24 041689 / / PHS HHS / United States