Genomic determinants of biological age estimated by deep learning applied to retinal images.

Journal: GeroScience
PMID: 39775603

Abstract

With the development of deep learning (DL) techniques, there has been a successful application of this approach to determine biological age from latent information contained in retinal images. Retinal age gap (RAG) defined as the difference between chronological age and predicted retinal age has been established previously to predict the age-related disease. In this study, we performed discovery genome-wide association analysis (GWAS) on the RAG using the 31,271 UK Biobank participants and replicated our findings in 8034 GoDARTS participants. The genetic correlation between RAGs predicted from the two cohorts was 0.67 (P = 0.021). After meta-analysis, we found 13 RAG loci which might be related to retinal vessel density and other aging processes. The SNP-wide heritability (h) of RAG was 0.15. Meanwhile, by performing Mendelian randomization analysis, we found that glycated hemoglobin, inflammation hemocytes, and anemia might be associated with accelerated retinal aging. Our study explored the biological implications and molecular-level mechanism of RAG, which might enable causal inference of the aging process as well as provide potential pharmaceutical intervention targets for further treatment.

Authors

  • Yu Huang
    School of Data Science and Software Engineering, Qingdao University, Qingdao 266021, China.
  • Mohammad Ghouse Syed
    VAMPIRE Project, Computer Vision and Image Processing Group, School of Science and Engineering (Computing), University of Dundee, Dundee, DD1 9SY, UK.
  • Ruiye Chen
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.
  • Cong Li
    Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, National Demonstration Center for Experimental Chemistry Education, Northwest University, Xi'an, Shaanxi 710127, China. Electronic address: licong@nwu.edu.cn.
  • Xianwen Shang
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.
  • Wei Wang
    State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
  • Xueli Zhang
    Center for Systems Biology, Soochow University, Suzhou 215006, Jiangsu, China.
  • Xiayin Zhang
    State Key Laboratory of Ophthalmology, Clinical Research Center for Ocular Disease, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, China.
  • Shulin Tang
    Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
  • Jing Liu
    Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
  • Shunming Liu
    Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
  • Sundar Srinivasan
    Division of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
  • Yijun Hu
    Aier Institute of Refractive Surgery, Refractive Surgery Center, Guangzhou Aier Eye Hospital, Guangzhou, China.
  • Muthu Rama Krishnan Mookiah
    Department of Electronics and Computer Engineering, Ngee Ann Polytechnic, Singapore 599489, Singapore. Electronic address: mkm2@np.edu.sg.
  • Huan Wang
    Key Laboratory of Adaptation and Evolution of Plateau Biota (AEPB), Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Qinghai, P. R. China.
  • Emanuele Trucco
  • Honghua Yu
    Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, the Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
  • Colin Palmer
    Division of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
  • Zhuoting Zhu
    Department of Ophthalmology, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China.
  • Alexander S F Doney
    Division of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK. a.doney@dundee.ac.uk.
  • Mingguang He
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China; Centre for Eye Research Australia; Departments of Ophthalmology and Surgery, University of Melbourne, Melbourne, Australia. Electronic address: mingguang.he@unimelb.edu.au.

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