Comprehensive search for Alzheimer disease susceptibility loci in the APOE region

Gyungah Jun, Badri N. Vardarajan, Jacqueline Buros, Chang En Yu, Michele V. Hawk, Beth A. Dombroski, Paul K. Crane, Eric B. Larson, Richard Mayeux, Jonathan L. Haines, Kathryn L. Lunetta, Margaret A. Pericak-Vance, Gerard D. Schellenberg, Lindsay A. Farrer

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Objective: To evaluate the association of risk and age at onset (AAO) of Alzheimer disease (AD) with single-ucleotide polymorphisms (SNPs) in the chromosome 19 region including apolipoprotein E (APOE) and a repeatlength 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.

Original languageEnglish (US)
Pages (from-to)1270-1279
Number of pages10
JournalArchives of neurology
Volume69
Issue number10
DOIs
StatePublished - Oct 1 2012

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Comprehensive search for Alzheimer disease susceptibility loci in the APOE region'. Together they form a unique fingerprint.

  • Cite this

    Jun, G., Vardarajan, B. N., Buros, J., Yu, C. E., Hawk, M. V., Dombroski, B. A., Crane, P. K., Larson, E. B., Mayeux, R., Haines, J. L., Lunetta, K. L., Pericak-Vance, M. A., Schellenberg, G. D., & Farrer, L. A. (2012). Comprehensive search for Alzheimer disease susceptibility loci in the APOE region. Archives of neurology, 69(10), 1270-1279. https://doi.org/10.1001/archneurol.2012.2052