Diana Jennifer Moreno1, Susana Ruiz1, Ángela Ríos2, Francisco Lopera3, Henry Ostos4, Marc Via5, Gabriel Bedoya1. 1. 1 Grupo de Genética Molecular, Universidad de Antioquia, Medellín, Colombia. 2. 2 Grupo de Neuropsicología, Universidad Surcolombiana, Neiva, Colombia. 3. 3 Grupo de Neurociencias, Universidad de Antioquia, Medellín, Colombia. 4. 4 Grupo de Medicina Genómica, Universidad Surcolombiana, Neiva, Colombia. 5. 5 Psicologia Clínica i Psicobiologia and Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
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.
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.