Association of GWAS Top Genes With Late-Onset Alzheimer's Disease in Colombian Population. (February 2017)

• Record Type: Journal Article
• Authors: Moreno, Diana Jennifer; Ruiz, Susana; Ríos, Ángela; Lopera, Francisco; Ostos, Henry; Via, Marc; Bedoya, Gabriel
• Is Part Of: American journal of Alzheimer's disease & other dementias. Volume 32:Number 1(2017)
• Page Start: 27
• Page End: 35
• Publication Date: 2017-02
• Subjects: susceptibility to late-onset Alzheimer's disease -- GWAS -- polymorphisms -- genetic interaction -- APOE∊4 -- genetic admixture; Alzheimer's disease -- Periodicals; Dementia -- Periodicals; Alzheimer's disease -- Patients -- Care -- United States -- Periodicals; 616.83
• DOI: 10.1177/1533317516679303
• Languages: English
• ISSNs: 1533-3175

Abstract

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, APOE∊4 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.