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Epidemiology
Clinical science
Metabolomic signature of retinal ageing, polygenetic susceptibility, and major health outcomes
  1. Riqian Liu1,
  2. Shaopeng Yang1,
  3. Xiaoying Zhong1,2,
  4. Ziyu Zhu1,
  5. Wenyong Huang1,3,
  6. Wei Wang1,3
  1. 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Study Center for Ocular Diseases, Sun Yat-Sen University, Guangzhou, Guangdong, China
  2. 2Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
  3. 3Hainan Eye Hospital and Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Haikou, China
  1. Correspondence to Wei Wang; wangwei{at}gzzoc.com

Abstract

Background/aims To identify the metabolic underpinnings of retinal aging and examine how it is related to mortality and morbidity of common diseases.

Methods The retinal age gap has been established as essential aging indicator for mortality and systemic health. We applied neural network to train the retinal age gap among the participants in UK Biobank and used nuclear magnetic resonance (NMR) to profile plasma metabolites. The metabolomic signature of retinal ageing (MSRA) was identified using an elastic network model. Multivariable Cox regressions were used to assess associations between the signature with 12 serious health conditions. The participants in Guangzhou Diabetic Eye Study (GDES) cohort were analyzed for validation.

Results This study included 110 722 participants (mean age 56.5±8.1 years at baseline, 53.8% female), and 28 plasma metabolites associated with retinal ageing were identified. The MSRA revealed significant correlations with each 12 serious health conditions beyond traditional risk factors and genetic predispositions. Each SD increase in MSRA was linked to a 24%–76% higher risk of mortality, cardiovascular diseases, dementia and diabetes mellitus. MSRA showed dose–response relationships with risks of these diseases, with seven showing non-linear and five showing linear increases. Validation in the GDES further established the relation between retinal ageing-related metabolites and increased risks of cardiovascular and chronic kidney diseases (all p<0.05).

Conclusions The metabolic connections between ocular and systemic health offer a novel tool for identifying individuals at high risk of premature ageing, promoting a more holistic view of human health.

  • Retina
  • Public health
  • Epidemiology
  • Genetics
  • Imaging

Data availability statement

All data used in this study are available from UK Biobank via data access procedures (http://www.ukbiobank.ac.uk). Permission to use the UK Biobank Resource was obtained via material transfer agreement as part of Application 105658. Not applicable.

https://doi.org/10.1136/bjo-2024-325846

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    Data availability statement

    All data used in this study are available from UK Biobank via data access procedures (http://www.ukbiobank.ac.uk). Permission to use the UK Biobank Resource was obtained via material transfer agreement as part of Application 105658. Not applicable.

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    Footnotes

    • RL, SY, XZ and ZZ are joint first authors.

    • Contributors WW designed the study. RL and WW performed the statistical analysis. WW, SY, XZ and RL interpreted the data. SY, ZZ, XZ, RL and WW interpreted the findings and drafted the manuscript. WW and WH supervised the study. All authors reviewed the manuscript, edited it for intellectual content and gave final approval for this version to be published. WW is the guarantor of this work and, as such, has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    • Funding Funding by Science and Technology Projects in Guangzhou (Guangzhou & University Jointly Basic Research Project, grant no. SL2024A03J00472).

    • Disclaimer The sponsor had no role in the study design and to conduct this research.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.