Genomic variation in educational attainment modifies Alzheimer’s disease risk

Abstract

ObjectiveTo determine the putative protective relationship of educational attainment on Alzheimers disease (AD) risk using Mendelian randomization, and to test the hypothesis that by using genetic regions surrounding individually associated SNPs as the instrumental variable we can identify genes that contribute to the relationship.\n\nMethodsWe performed Mendelian randomization using genome-wide association study summary statistics from studies of educational attainment and AD in two stages. Our instrumental variable comprised of i) 1,271 SNPs significantly associated with educational attainment and ii) individual 2Mb regions surrounding the genome-wide significant SNPs.\n\nResultsA causal inverse relationship between educational attainment and AD was identified by the 1,271 SNPs (odds ratio = 0.63; 95% CI, 0.54-0.74; p =4.08x10-8). Analysis of individual loci identified six regions that significantly replicated the causal relationship. Genes within these regions included LRRC2, SSBP2, and NEGR1; the latter a regulator of neuronal growth.\n\nConclusionsEducational attainment is an important protective factor for AD. Genomic regions that significantly paralleled the overall causal relationship contain genes expressed in neurons or involved in the regulation of neuronal development.