Autoencoder-based phenotyping of ophthalmic images highlights genetic loci influencing retinal morphology and provides informative biomarkers

Bioinformatics. 2024 Dec 26;41(1):btae732. doi: 10.1093/bioinformatics/btae732.

Abstract

Motivation: Genome-wide association studies (GWAS) have been remarkably successful in identifying associations between genetic variants and imaging-derived phenotypes. To date, the main focus of these analyses has been on established, clinically-used imaging features. We sought to investigate if deep learning approaches can detect more nuanced patterns of image variability.

Results: We used an autoencoder to represent retinal optical coherence tomography (OCT) images from 31 135 UK Biobank participants. For each subject, we obtained a 64-dimensional vector representing features of retinal structure. GWAS of these autoencoder-derived imaging parameters identified 118 statistically significant loci; 41 of these associations were also significant in a replication study. These loci encompassed variants previously linked with retinal thickness measurements, ophthalmic disorders, and/or neurodegenerative conditions. Notably, the generated retinal phenotypes were found to contribute to predictive models for glaucoma and cardiovascular disorders. Overall, we demonstrate that self-supervised phenotyping of OCT images enhances the discoverability of genetic factors influencing retinal morphology and provides epidemiologically informative biomarkers.

Availability and implementation: Code and data links available at https://github.com/tf2/autoencoder-oct.

MeSH terms

  • Biomarkers
  • Deep Learning
  • Genetic Loci*
  • Genome-Wide Association Study* / methods
  • Glaucoma / diagnostic imaging
  • Glaucoma / genetics
  • Humans
  • Phenotype*
  • Polymorphism, Single Nucleotide
  • Retina* / diagnostic imaging
  • Tomography, Optical Coherence* / methods

Substances

  • Biomarkers