DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Alzheimer's disease (late onset). The EFO term Alzheimers disease was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: Alzheimers disease

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

EM Reiman, JA Webster, AJ Myers, J Hardy, T Dunckley, VL Zismann, KD Joshipura, JV Pearson, D Hu-Lince, MJ Huentelman, DW Craig, KD Coon, WS Liang, RH Herbert, T Beach, KC Rohrer, AS Zhao, D Leung, L Bryden, L Marlowe, M Kaleem, D Mastroeni, A Grover, CB Heward, R Ravid, J Rogers, ML Hutton, S Melquist, RC Petersen, GE Alexander, RJ Caselli, W Kukull, A Papassotiropoulos, DA Stephan

TITLE:

GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers.

JOURNAL:

Neuron Jun 2007, Vol 54, pp. 713-20

ABSTRACT:

The apolipoprotein E (APOE) epsilon4 allele is the best established genetic risk factor for late-onset Alzheimer's disease (LOAD). We conducted genome-wide surveys of 502,627 single-nucleotide polymorphisms (SNPs) to characterize and confirm other LOAD susceptibility genes. In epsilon4 carriers from neuropathologically verified discovery, neuropathologically verified replication, and clinically characterized replication cohorts of 1411 cases and controls, LOAD was associated with six SNPs from the GRB-associated binding protein 2 (GAB2) gene and a common haplotype encompassing the entire GAB2 gene. SNP rs2373115 (p = 9 x 10(-11)) was associated with an odds ratio of 4.06 (confidence interval 2.81-14.69), which interacts with APOE epsilon4 to further modify risk. GAB2 was overexpressed in pathologically vulnerable neurons; the Gab2 protein was detected in neurons, tangle-bearing neurons, and dystrophic neuritis; and interference with GAB2 gene expression increased tau phosphorylation. Our findings suggest that GAB2 modifies LOAD risk in APOE epsilon4 carriers and influences Alzheimer's neuropathology. PUBMED: 17553421
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