Association of GWAS Top Genes With Late-Onset Alzheimer's Disease in Colombian Population

作者：Jennifer Moreno Diana; Ruiz Susana; Rios Angela; Lopera Francisco; Ostos Henry; Via Marc; Bedoya Gabriel

来源：American Journal of Alzheimer's Disease and Other Dementias, 2017, 32(1): 27-35.

DOI：10.1177/1533317516679303

• susceptibility to late-onset Alzheimer's disease
• GWAS
• polymorphisms
• genetic interaction
• APOE4
• genetic admixture

Objective: The association of variants in CLU, CR1, PICALM, BIN1, ABCA7, and CD33 genes with late-onset Alzheimer's disease (LOAD) was evaluated and confirmed through genome-wide association study. However, it is unknown whether these associations can be replicated in admixed populations.
Methods: The association of 14 single-nucleotide polymorphisms in those genes was evaluated in 280 LOAD cases and 357 controls from the Colombian population.
Results: In a multivariate analysis using age, gender, APOE4 status, and admixture covariates, significant associations were obtained (P < .05) for variants in BIN1 (rs744373, odds ratio [OR]: 1.42), CLU (rs11136000, OR: 0.66), PICALM (rs541458, OR: 0.69), ABCA7 (rs3764650, OR: 1.7), and CD33 (rs3865444, OR: 1.12). Likewise, a significant interaction effect was observed between CLU and CR1 variants with APOE.
Conclusion: This study replicated the associations previously reported in populations of European ancestry and shows that APOE variants have a regulatory role on the effect that variants in other loci have on LOAD, reflecting the importance of gene-gene interactions in the etiology of neurodegenerative diseases.

• 出版日期2017-2