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P4‐105: The GAB2 gene and the risk of Alzheimer's disease: Replication and meta‐analysis
Author(s) -
Ikram Mohammad A.,
Liu Fan,
Oostra Ben A.,
Hofman Albert,
Duijn Cornelia M.,
Breteler Monique M.B.
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.773
Subject(s) - meta analysis , odds ratio , population stratification , genotyping , apolipoprotein e , dementia , rotterdam study , allele , disease , medicine , population , oncology , genetics , genotype , bioinformatics , biology , single nucleotide polymorphism , gene , environmental health
Recently, GAB2 has been suggested to modify the risk of late-onset Alzheimer's disease (AD) among APOEepsilon4 carriers. However, replication data are inconsistent.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.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.We found GAB2 to be associated with AD. Furthermore, the meta-analysis also suggests that GAB2 modifies the risk of AD in APOEepsilon4 carriers.