Replicative Analysis Of 30 Snps In Russian Patients With Alzheimer’s Disease

Background Alzheimer’s disease is a highly heritable genetically heterogeneous disorder with 60%–80% of risk attributed to genetic factors. Two forms of the disease are known as Early-onset familial Alzheimer's disease and Late-onset sporadic Alzheimer's disease. Although scientists know how brain cells of persons with Alzheimer's disease are affected, and additionally understand some of the genetic explanations of the disease, the precise cause of this disease is still unclear. There are over 90 Genome-Wide Association Studies for Alzheimer's disease. However, only a few associations were replicated in independent data. The aim of this study was to analyze associations of 30 SNPs reported in GWAS with Alzheimer’s disease in Russian population of Siberian region. Methods 108 patients with AD and 285 healthy controls, matched to the patients by age, gender, and ethnicity were included in this study. 30 SNPs were genotyped by MALDI-TOF mass-spectrometry using MassARRAY Analyzer 4 (Sequenom). Allele-specific ORs and associated p-values were calculated. Results We found three significant associations of SNPs with AD in Russian patients of Siberian region: rs17594526 at TCF4 gene (OR = 1.77, p=0.003), rs11064768 at CCDC60 gene (OR = 2.15, p= 0.02) and rs12922317 at SNX29 gene (OR = 1.47, p= 0.02). These genetic markers were previously reported in GWAS associated with schizophrenia. Discussion Only the TCF4 gene has known functional importance for cognitive dysfunctions of schizophrenia and Alzheimer's disease. As a transcription factor, the TCF4 gene regulates the expression of other genes involved in cell differentiation, survival, and neurodevelopment. Genetic markers of CCDC60 and SNX29 are associated with Alzheimer’s disease but their role in pathogenesis of the disease is not clear. This work was supported by the Russian Science Foundation (project # 16-14-00020).