Overlapping Pattern of Genetic Associations of Alzheimer’s Disease And Schizophrenia Mediated By Cognitive Endophenotypes Genes

Background Replicative analysis of genetic markers, previously identified in genome-wide association studies (GWAS) for neuropsychiatric diseases, in population of various origin may contribute to better understanding of genetic composition of the diseases. Methods In this study 50 SNPs found in GWAS for schizophrenia (SZ), Alzheimer’s diseases (AD) and cognitive endophenotypes were genotyped in patients and control samples from Russian and Kazakh populations. Genotyping was performed by TaqMan assays and MALDI-TOF mass-spectrometry. Results Eight polymorphic markers (SNPs in regions of genes for APOЕ, APOJ, CSMD1, CCDC60, SNX29, PICALM, NOTCH4 and NRIP1) were associated with AD in Russian population. Associations of 10 genetic markers with SZ in Russian populations (markers in regions of genes for NRGN, KCNB2, NRIP1, CCDC60, LSM1, LOC100129100 / LOC100509857, CSMD1, СPVL, POM121L2 and NDE1P1 / PRMT6) and 8 genetic markers in Kazakh population (VRK2, KCNB2, СPVL, BRD1, PVRL2, ARHGAP1, CD33 и GPR89P / TRV-AAC1-5) were replicated. Multidimensional reduction methods revealed epistatic interaction of several genetic loci in formation of susceptibility to SZ in populations of various ethnic origin. Discussion Overlapping fields of genetic associations for AD and SZ, demonstrating some similarity in inherited background for both diseases, were found. This interaction may be implemented through common unknown levels in pathogenesis of AD and SZ, mediated by cognitive endophenotypes. Bioinformatic analysis of biological functions of associated genes revealed that among primary biological processes enriched by genes under study are the processes of lipid metabolism, cellular interactions, various regulatory and transport processes in neural cells, processes of immune response regulation. Substantial part of investigated genes forms an interacting network, which consisted of distinct clusters corresponding to major biological processes, were genes under study are involved, and to basic molecular functions of their products. Data obtained in the project, extend the understanding of genetic component in neuro-psychiatric diseases, as well as the biological processes and functions, implemented in the manifestation of genetic susceptibility to AD and SZ.