Comprehensive Search for Alzheimer Disease Susceptibility Loci in the APOE Region.
Jun, Gyungah PhD; Vardarajan, Badri N. PhD; Buros, Jacqueline BA; Yu, Chang-En PhD; Hawk, Michele V. DVM; Dombroski, Beth A. PhD; Crane, Paul K. MD, MPH; Larson, Eric B. MD, MPH; Alzheimer's Disease Genetics Consortium; Mayeux, Richard MD, MS; Haines, Jonathan L. PhD; Lunetta, Kathryn L. PhD; Pericak-Vance, Margaret A. PhD; Schellenberg, Gerard D. PhD; Farrer, Lindsay A. PhD
[Article]
Archives of Neurology.
69(10):1270-1279, October 2012.
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Objective: To evaluate the association of risk and age at onset (AAO) of Alzheimer disease (AD) with single-nucleotide polymorphisms (SNPs) in the chromosome 19 region including apolipoprotein E (APOE) and a repeat-length polymorphism in TOMM40 (poly-T, rs10524523).
Design: Conditional logistic regression models and survival analysis.
Setting: Fifteen genome-wide association study data sets assembled by the Alzheimer's Disease Genetics Consortium.
Participants: Eleven thousand eight hundred forty AD cases and 10 931 cognitively normal elderly controls.
Main Outcome Measures: Association of AD risk and AAO with genotyped and imputed SNPs located in an 800-Mb region including APOE in the entire Alzheimer's Disease Genetics Consortium data set and with the TOMM40 poly-T marker genotyped in a subset of 1256 cases and 1605 controls.
Results: In models adjusting for APOE [epsilon]4, no SNPs in the entire region were significantly associated with AAO at P < .001. Rs10524523 was not significantly associated with AD or AAO in models adjusting for APOE genotype or within the subset of [epsilon]3/[epsilon]3 subjects.
Conclusions: APOE alleles [epsilon]2, [epsilon]3, and [epsilon]4 account for essentially all the inherited risk of AD associated with this region. Other variants including a poly-T track in TOMM40 are not independent risk or AAO loci.
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