Comprehensive search for Alzheimer disease susceptibility loci in the APOE region.
Ontology highlight
ABSTRACT: 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 ε4, 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 ε3/ε3 subjects.Conclusions
APOE alleles ε2, ε3, and ε4 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.
SUBMITTER: Jun G
PROVIDER: S-EPMC3579659 | biostudies-literature | 2012 Oct
REPOSITORIES: biostudies-literature
Publications
Comprehensive search for Alzheimer disease susceptibility loci in the APOE region.
Jun Gyungah G Vardarajan Badri N BN Buros Jacqueline J Yu Chang-En CE Hawk Michele V MV Dombroski Beth A BA Crane Paul K PK Larson Eric B EB Mayeux Richard R Haines Jonathan L JL Lunetta Kathryn L KL Pericak-Vance Margaret A MA Schellenberg Gerard D GD Farrer Lindsay A LA
Archives of neurology 20121001 10
<h4>Objective</h4>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).<h4>Design</h4>Conditional logistic regression models and survival analysis.<h4>Setting</h4>Fifteen genome-wide association study data sets assembled by the Alzheimer's Disease Genetics Consortium.<h4>Participants</h4>Eleven th ...[more]
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