iGWAS: Image-based genome-wide association of self-supervised deep phenotyping of retina fundus images.

Existing imaging genetics studies have been mostly limited in scope by using imaging-derived phenotypes defined by human experts. Here, leveraging new breakthroughs in self-supervised deep representation learning, we propose a new approach, image-based genome-wide association study (iGWAS), for identifying genetic factors associated with phenotypes discovered from medical images using contrastive learning. Using retinal fundus photos, our model extracts a 128-dimensional vector representing features of the retina as phenotypes. After training the model on 40,000 images from the EyePACS dataset, we generated phenotypes from 130,329 images of 65,629 British White participants in the UK Biobank. We conducted GWAS on these phenotypes and identified 14 loci with genome-wide significance (p<5×10−8 and intersection of hits from left and right eyes). We also did GWAS on the retina color, the average color of the center region of the retinal fundus photos. The GWAS of retina colors identified 34 loci, 7 are overlapping with GWAS of raw image phenotype. Our results establish the feasibility of this new framework of genomic study based on self-supervised phenotyping of medical images. Author summary: Imaging genetics is a research field focused on understanding how genetic variations influence observable traits or diseases that can be visualized through medical imaging. Previous studies in imaging genetics have mostly relied on traits identified by human experts. In this study, we used a self-supervised contrastive learning algorithm that automatically identifies features in fundus images that are unique to each individual yet consistent between their left and right eyes. These features are represented as a set of 128 numbers that can quantitatively describe the characteristics of each individual's fundus images without human labeling bias. We then conducted genome wide association studies (GWAS) to explore the associations between these features and genetic variations using paired fundus images and genetic data from the UK Biobank. Our findings indicate that these features are linked to genetic signals associated with eye measurements, eye diseases, pigmentation, and vessel development. Additionally, we found that GWAS of this set of features identified new genetic signals not detected in GWAS only using retina color. These results establish the feasibility of this self-supervised phenotyping approach for imaging genetics studies. [ABSTRACT FROM AUTHOR]