Shared genetic architecture between the two neurodegenerative diseases: Alzheimer’s disease and glaucoma

作者：Chunwen Zheng, Shunming Liu, Xiayin Zhang, Xiayin Zhang, Yunyan Hu, Xianwen Shang, Zhuoting Zhu, Yu Huang, Guanrong Wu, Yu Xiao, Zijing Du, Yingying Liang, Daiyu Chen, Siwen Zang, Yijun Hu, Mingguang He, Xueli Zhang, Xueli Zhang, Honghua Yu · 发表于：Frontiers in Aging Neuroscience · 年份：2022 · DOI：10.3389/fnagi.2022.880576 · 被引用次数：21 · 研究领域：Glaucoma and retinal disorders、Alzheimer's disease research and treatments、Retinal Development and Disorders

Background Considered as the representatives of neurodegenerative diseases, Alzheimer’s disease (AD) and glaucoma are complex progressive neuropathies affected by both genetic and environmental risk factors and cause irreversible damages. Current research indicates that there are common features between AD and glaucoma in terms of epidemiology and pathophysiology. However, the understandings and explanations of their comorbidity and potential genetic overlaps are still limited and insufficient. Method Genetic pleiotropy analysis was performed using large genome-wide association studies summary statistics of AD and glaucoma, with an independent cohort of glaucoma for replication. Conditional and conjunctional false discovery rate methods were applied to identify the shared loci. Biological function and network analysis, as well as the expression level analysis were performed to investigate the significance of the shared genes. Results A significant positive genetic correlation between AD and glaucoma was identified, indicating that there were significant polygenetic overlaps. Forty-nine shared loci were identified and mapped to 11 shared protein-coding genes. Functional genomic analyses of the shared genes indicate their modulation of critical physiological processes in human cells, including those occurring in the mitochondria, nucleus, and cellular membranes. Most of the shared genes indicated a potential modulation of metabolic processes in human cells and tissues. Furtherm...