Abstract
Alzheimer’s disease (AD) is a common neurodegenerative disease with high morbidity among elderly people. A genetic attribution has been extensively proved. Here, we propose to further prioritize genes that harbor single nucleotide variation (SNV) or structural variation (SV) for AD and explore the underlying potential mechanisms through exploiting their expression and methylation spectra. A high-confidence AD-associated candidate gene list was obtained from the ClinVar and Human Gene Mutation Database (HGMD). Genome-wide methylation and expression profiles of AD and normal subjects were downloaded from the Gene Expression Omnibus (GEO). Through comprehensive comparison of expression and methylation levels between AD and normal samples, as well as different stages of AD samples, SORL1 was identified as the most plausible gene for AD incidence and progression. Gene Set Enrichment Analysis (GSEA) revealed significant activation of the ABC (ATP binding cassette) transporter with the aberrant up-regulation of SORL1 within AD samples. This study unfolds the expression and methylation spectra of previously probed genes with SNV or SV in AD for the first time, and reports an aberrant activation of the ABC transporter pathway that might contribute to AD progression. This should shed some light on AD diagnosis and precision treatment.
Funding source: Tianjin Natural Science Foundation of China
Award Identifier / Grant number: 16JCYBJC25500
Funding source: The key project in the Science and Technology Foundation of Tianjin Health and Family Planning
Award Identifier / Grant number: 15KG136
Funding source: Tianjin Science and Technology Commission Scientific Popularization Project
Award Identifier / Grant number: 17KPHDSF00170
Author contributions: All authors have made contributions to this research and the authors’ contribution is below. WZQ, QXD and LX, put forward the ideas of this article, wrote this article and analyzed the data.CY, XXS, ZBY, SXG and ZGM, helped in the acquisition of data and put forward the ideas of the article.WL, ZQ, XC, JSH, LXL, XBX, LXH and AZ helped in the analysis and interpretation of data and in revising the manuscript. WZQ, ZSJ, LX, provided valuable instructions and suggestions for this paper and helped in revising the manuscript.
Research funding: This study was funded by Tianjin Natural Science Foundation of China (Grant No. 16JCYBJC25500), the key project in the Science and Technology Foundation of Tianjin Health and Family Planning (Grant No. 15KG136) and Tianjin Science and Technology Commission Scientific Popularization Project (Grant No. 17KPHDSF00170).
Conflict of interest: No competing financial interests exist.
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Supplementary material
The online version of this article offers supplementary material (https://doi.org/10.1515/znc-2019-0213).
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