Association and Gene-Gene Interactions Study of Late-Onset Alzheimer's Disease in the Russian Population.

Anna Bocharova,Oksana Makeeva,Irina Zhukova,Andrey Marusin,Vadim Stepanov,Kseniya Vagaitseva,Natalia Zhukova,Larisa Minaycheva

doi:10.3390/genes12101647

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder, and represents the most common cause of dementia. In this study, we performed several different analyses to detect loci involved in development of the late onset AD in the Russian population. DNA samples from 472 unrelated subjects were genotyped for 63 SNPs using iPLEX Assay and real-time PCR. We identified five genetic loci that were significantly associated with LOAD risk for the Russian population (TOMM40 rs2075650, APOE rs429358 and rs769449, NECTIN rs6857, APOE ε4). The results of the analysis based on comparison of the haplotype frequencies showed two risk haplotypes and one protective haplotype. The GMDR analysis demonstrated three significant models as a result: a one-factor, a two-factor and a three-factor model. A protein–protein interaction network with three subnetworks was formed for the 24 proteins. Eight proteins with a large number of interactions are identified: APOE, SORL1, APOC1, CD33, CLU, TOMM40, CNTNAP2 and CACNA1C. The present study confirms the importance of the APOE-TOMM40 locus as the main risk locus of development and progress of LOAD in the Russian population. Association analysis and bioinformatics approaches detected interactions both at the association level of single SNPs and at the level of genes and proteins.

Highlights

Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia
The minor allele frequencies of 58 SNPs in LOAD patients and in controls are presented in a Table 2
The statistical power of the study was estimated for the Genetic Association Study (GAS) Power Calculator assuming an odds ratio (Genotype Relative Risk) of 1.5, allele frequencies 18% in AD cases, and a significance level of 0.05

Summary

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia. The disease is characterized by the loss of neurons and synaptic connections in the cortex and certain subcortical areas. AD is clinically characterized by decline in progressive executive function, perceptual speed, short-term memory and other cognitive capacities [1]. Degradation of cognitive functions has a major impact on an individual’s quality of life. According to the World Alzheimer Report 2018, there are over 50 million people suffering from AD or other dementias in the world [2]. Approximately 5–7 million new cases of AD are registered in the geriatric population [3]

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