Identification of candidate genes associated with clinical onset of Alzheimer's disease

Wang Liao; Haoyu Luo; Yuting Ruan; Yingren Mai; Chongxu Liu; Jiawei Chen; Shaoqing Yang; Aiguo Xuan; Jun Liu

doi:10.3389/fnins.2022.1060111

Identification of candidate genes associated with clinical onset of Alzheimer's disease

Front Neurosci. 2022 Dec 20:16:1060111. doi: 10.3389/fnins.2022.1060111. eCollection 2022.

Authors

Wang Liao¹, Haoyu Luo¹, Yuting Ruan², Yingren Mai¹, Chongxu Liu¹, Jiawei Chen³, Shaoqing Yang¹, Aiguo Xuan⁴, Jun Liu¹

Affiliations

¹ Department of Neurology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
² Department of Rehabilitation, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
³ Guangzhou Medical University, Guangzhou, China.
⁴ School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.

Abstract

Background and objective: Alzheimer's disease (AD) is the most common type of dementia, with its pathology like beta-amyloid and phosphorylated tau beginning several years before the clinical onset. The aim is to identify genetic risk factors associated with the onset of AD.

Methods: We collected three microarray data of post-mortem brains of AD patients and the healthy from the GEO database and screened differentially expressed genes between AD and healthy control. GO/KEGG analysis was applied to identify AD-related pathways. Then we distinguished differential expressed genes between symptomatic and asymptomatic AD. Feature importance with logistic regression analysis is adopted to identify the most critical genes with symptomatic AD.

Results: Data was collected from three datasets, including 184 AD patients and 132 healthy controls. We found 66 genes to be differently expressed between AD and the control. The pathway enriched in the process of exocytosis, synapse, and metabolism and identified 19 candidate genes, four of which (VSNL1, RTN1, FGF12, and ENC1) are vital.

Conclusion: VSNL1, RTN1, FGF12, and ENC1 may be the essential genes that progress asymptomatic AD to symptomatic AD. Moreover, they may serve as genetic risk factors to identify high-risk individuals showing an earlier onset of AD.

Keywords: Alzheimer’s disease; GEO; dementia; genes; transcriptomic analysis.