Replicative association analysis of genetic markers of cognitive traits with Alzheimer’s disease in the Russian population

Abstract

Replicative association analysis of Alzheimer's disease (AD) with 15 genetic markers associated with cognitive traits in genome-wide association studies was performed. In a Russian populations associations of rs2616984 in CSMD1 gene with AD (OR = 1.50, 95% CI = 1.07-2.09, p-value = 0.018) and putative associations with the disease of rs3131296 in NOTCH4 gene (OR = 1.53, 95% CI = 0.98-2.39, p-value = 0.06) and rs2229741 of NRIP1 gene (OR = 1.35, CI = 0.99-1.85, p-value = 0.061) were revealed. Combinations of epistatic interacting genes (CSMD1 and NRIP1; NOTCH4, CSMD1 and NRIP1; TLR4, CSMD1 and NRIP1) were found, as well as their genotypes combinations significantly associated with AD and characterized by highest predictive values. Probable molecular mechanisms implicated in the relation of genes under study to AD pathogenesis are discussed. Bioinformatic analysis of biological processes, molecular functions and protein-protein interactions of BA genes demonstrated that genes under study may play modulating and modifying role by participation in various regulatory and signal pathways involved in a disease development.