Targeted Sequencing of Alzheimer’s Disease Genes in Gujarat Cohort

Abstract

AbstractAlzheimer’s Disease (AD) is the most common type of dementia affecting cognitive and behavioural functions. It’s a complex disease that results from the modest effect of gene interaction and environmental factors, as a result of which its exact pathogenesis is still unknown. In the present study, we have performed an association study of exonic regions of 94 genes with AD using the Haloplex target enrichment method and genotyping of 4 genes NOTCH4(rs367398), NEP(rs61760379), APOE (rs121918398), and ATP7B(rs1801243) using PCR RFLP technique. In this study, we screened 32 AD cases and 11 control samples. We have identified 19 variants assigned to 16 genes that were significantly associated with AD with a p-value < 0.05. However, no variants have passed multiple test corrections except NOTCH4/rs367398 genotyped using the PCR-RFLP approach. The functional enrichment analysis of the significant genes for the disease indicates that the genes are significantly involved in AD. Also, functional enrichment analysis for biological processes using ClueGo and network analysis using the STRING database indicated that the genes are directly and indirectly playing a role in AD pathogenesis. The eQTL analysis of the variants with GTEx dataset indicate that out of 19 variants ACHE/rs1799806 and NOTCH4/rs367398 variants is showing significant eQTL for the neighbouring genes for different brain regions and whole blood. Regardless, additional studies with a large cohort are required to establish the role and prevalence of these variants in the local population of Gujarat.