Genetic Ancestry and Accumulation of BIN1 Gene Risk Alleles Associated to Alzheimer’s Disease in Latin American Populations

Abstract

BIN1 gene is the second highest associated locus to Alzheimer’s disease (AD). Association between genetic ancestry and susceptibility to AD have been found for APOE, the principal genetic risk factor for AD. However, there is a lack of studies on this relationship for BIN1, which is the aim of this work, focused in four Latin American populations. The individual proportions of genetic ancestry were estimated by using a SNP panel previously proposed and optimized for Latin American populations. Three models were set: a risk allele dominant model, a non-risk allele dominant model and a codominant model. The Poisson regression analysis was applied to the risk allele accumulation and logistic regresìsion to a SNP by SNP model. The Poisson regression models tests showed that the accumulation of risk alleles was associated to ancestry as follow: an increasing risk effect for African in both codominance and dominant models, and a protective effect for Native-American for the risk allele dominant model. In the logistic regression analyses, association to individual genetic ancestry proportions for both models was found for rs17014923 and rs6743470, with negative association for Native American ancestry and positive for African and European. rs744373, showed an opposite pattern: positive association for Native-American ancestry and negative for European. Finally, positive association for African ancestry in Peruvian population at rs17014923. These results suggest an overall protective effect for Native-American ancestry and a risk effect for African ancestry in the Latin American sample, even if some particular SNPs shows an opposite pattern.