The GAB2 gene and the risk of Alzheimer's disease: replication and meta-analysis.
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.
Ikram
M Arfan
MA
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam 3000 CA, The Netherlands.
Liu
Fan
F
Oostra
Ben A
BA
Hofman
Albert
A
van Duijn
Cornelia M
CM
Breteler
Monique M B
MM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D048868:Adaptor Proteins, Signal Transducing; D001057:Apolipoproteins E; C490895:GAB2 protein, human