Decoding the genetic comorbidity network of Alzheimer's disease

Xueli Zhang; Dantong Li; Siting Ye; Shunming Liu; Shuo Ma; Min Li; Qiliang Peng; Lianting Hu; Xianwen Shang; Mingguang He; Lei Zhang

doi:10.1186/s13040-024-00394-w

Decoding the genetic comorbidity network of Alzheimer's disease

BioData Min. 2024 Oct 9;17(1):40. doi: 10.1186/s13040-024-00394-w.

Authors

Xueli Zhang^#^{1

2

3}, Dantong Li^#^{4

5}, Siting Ye^#^{6

7}, Shunming Liu^#⁸, Shuo Ma^{9

10}, Min Li⁴, Qiliang Peng^{11

12}, Lianting Hu⁵, Xianwen Shang^{13

14}, Mingguang He^{15

16}, Lei Zhang^{17

18

19}

Affiliations

¹ Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China. zhangxueli@gdph.org.cn.
² Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China. zhangxueli@gdph.org.cn.
³ Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, 510080, China. zhangxueli@gdph.org.cn.
⁴ Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
⁵ Medical Big Data Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
⁶ Department of Ultrasound, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
⁷ Department of Orthopaedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
⁸ Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
⁹ Clinical Data Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
¹⁰ Department of Ethicon Minimally Invasive Procedures and Advanced Energy, Johnson & Johnson Medical (Shanghai) Device Company, Shanghai, China.
¹¹ Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
¹² Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.
¹³ Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China. andy243@126.com.
¹⁴ Experimental Ophthalmology, The Hong Kong Polytechnic University, Hong Kong, People's Republic of China. andy243@126.com.
¹⁵ Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China. mingguang.he@polyu.edu.hk.
¹⁶ Experimental Ophthalmology, The Hong Kong Polytechnic University, Hong Kong, People's Republic of China. mingguang.he@polyu.edu.hk.
¹⁷ Clinical Medical Research Center, Children's Hospital of Nanjing Medical University, Nanjing, China. lei.zhang1@monash.edu.
¹⁸ School of Translational Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia. lei.zhang1@monash.edu.
¹⁹ Artificial Intelligence and Modelling in Epidemiology Program, Melbourne Sexual Health Centre, Alfred Health, Melbourne, Australia. lei.zhang1@monash.edu.

^# Contributed equally.

Abstract

Alzheimer's disease (AD) has emerged as the most prevalent and complex neurodegenerative disorder among the elderly population. However, the genetic comorbidity etiology for AD remains poorly understood. In this study, we conducted pleiotropic analysis for 41 AD phenotypic comorbidities, identifying ten genetic comorbidities with 16 pleiotropy genes associated with AD. Through biological functional and network analysis, we elucidated the molecular and functional landscape of AD genetic comorbidities. Furthermore, leveraging the pleiotropic genes and reported biomarkers for AD genetic comorbidities, we identified 50 potential biomarkers for AD diagnosis. Our findings deepen the understanding of the occurrence of AD genetic comorbidities and provide new insights for the search for AD diagnostic markers.