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BACKGROUND: Recently, GAB2 has been suggested to modify the risk of late-onset Alzheimer's disease (AD) among APOEepsilon4 carriers. However, replication data are inconsistent. METHODS: In a population-based cohort study (n = 5507; age > 55) with 443 incident AD cases, we investigated the association between rs4945261 and AD. Because we used high-density genotyping, we also investigated other polymorphisms within and around GAB2 and performed a meta-analysis with published studies. RESULTS: We found that rs4945261 was associated with AD among APOEepsilon4 carriers (p = .02) but not among noncarriers (p = .26). Fifteen of the 20 remaining polymorphisms within GAB2 and several polymorphisms in the 250kbp-region surrounding GAB2 were also associated with AD among carriers and only one among noncarriers. For rs2373115, meta-analysis yielded an odds ratio of 1.58 (1.17-2.14) with p = 3.0 * 10(-3) among carriers and 1.09 (.97-1.23) with p = .16 among noncarriers. For rs4945261, the pooled odds ratio was 1.75 (1.21-2.55) with p = 3.0 * 10(-3) among carriers and 1.20 (1.01-1.41) with p = .03 among noncarriers. CONCLUSIONS: We found GAB2 to be associated with AD. Furthermore, the meta-analysis also suggests that GAB2 modifies the risk of AD in APOEepsilon4 carriers.

Original publication

DOI

10.1016/j.biopsych.2008.11.014

Type

Journal article

Journal

Biol Psychiatry

Publication Date

01/06/2009

Volume

65

Pages

995 - 999

Keywords

Adaptor Proteins, Signal Transducing, Aged, Alzheimer Disease, Apolipoproteins E, Chi-Square Distribution, DNA Mutational Analysis, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Male, Mental Status Schedule, Meta-Analysis as Topic, Middle Aged, Polymorphism, Genetic, Risk Factors