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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

Biological psychiatry

Publication Date

06/2009

Volume

65

Pages

995 - 999

Addresses

Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam 3000 CA, The Netherlands.

Keywords

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