Methylation-wide association analysis reveals AIM2, DGUOK, GNAI3, and ST14 genes as potential contributors to the Alzheimer’s disease pathogenesis

Abstract

Introduction: Alzheimers disease (AD) is a progressive complex neurodegenerative disorder with devastating impact on cognitive abilities. It is among the top 10 leading causes of death in the United States with no curative medications. Exploring genetic and non-genetic contributors to AD development is, therefore, of great importance.\n\nMethods: We investigated the AD-associated epigenetic changes by combing results from publicly available genome-wide association analyses and a large-scale methylation quantitative trait loci study.\n\nResults: Probes mapped to 133 genes were associated with AD with < 2.50E-06. Of these, four genes (i.e., GNAI3, AIM2, DGUOK and ST14) provided stronger evidence of possible role in AD pathogenesis as they were also significantly associated with AD in previous expression quantitative trait loci analyses and/or mouse model studies.\n\nDiscussion: Although the identified associations do not prove any definitive causal relationships with AD, they provide a list of prioritized genes for follow-up functional studies.