Researchers examined imaging and genetic data from the UK Biobank to learn more about rare eye diseases. These include retinal dystrophies, a category of inherited retinal abnormalities that are the main reason working-age adults are documented as visually impaired.
The retina is located at the back of the eye. It is a layered tissue that absorbs light and converts it into a signal that the brain can understand. Within each retinal layer are several types of cells, each playing a specific role in this light conversion process.
The main subject of this study, published in the journal PLOS Genetics, are photoreceptor cells (PRCs), which are light-sensing cells found in the retina. These cells can now be visualized non-invasively with optical coherence tomography (OCT), a service frequently provided by many opticians. The largest genome-wide association analysis of PRCs was created by the researchers using OCT imaging data and genomic information held in the UK Biobank.
Uncommon Retinal Dystrophies
Inherited mutations in genes expressed by PRCs often lead to rare retinal disorders. These mutations can lead to retinal dysfunction, resulting in reduced vision and even blindness. Although each of these conditions is rare, taken as a whole they account for most of the blindness of individuals of working age.
Hannah Currant, a former doctoral student at EMBL's European Institute for Bioinformatics (EMBL-EBI) and postdoctoral researcher at the Novo Nordisk Foundation Protein Research Center (CPR) at the University of Copenhagen, said: We had access to combined images and genotype data at an unprecedented scale. The study's ability to find genetic links to rare retinal dystrophies was made possible by the study's fundamental reliance on access to this large amount of data. This discovery has opened up new directions for study and raised new concerns about rare retinal dystrophies.
High-resolution images of many layers and components of the retina can be found using OCT to link genotype and phenotype. In the clinic, these pictures are often used to help diagnose eye problems. This study used OCT scans of approximately 30.000 participants and relevant genetic and medical data from UK Biobank.
Ewan Birney, Deputy Director General of the European Institute of Molecular Biology, described the UK Biobank as “a rich and unique resource with great potential to enable genomic medicine” (EMBL). The data here has enormous potential to be uncovered to help us better understand human biology and how and why that biology is disrupted in disease.
Supporting Genomic Medicine
The researchers conducted genome-wide association analyzes (GWAS) on data from UK Biobank to identify genetic changes associated with variations in PRC layer thickness. As a result, they were able to discover genetic variants associated with the thickness of one or more PRC layers, including those linked to previously well-known eye diseases.
The GWAS Catalog stores and provides open access to recently discovered genetic correlations.
Many of these genetic variations were known to be associated with eye disorders, but interestingly, many were located near genes that, when disrupted, cause rare inherited eye diseases. In one example, the researchers had the opportunity to investigate how common variation combinations close to genes known to be associated with rare eye diseases alter the structure of the retina. This raises confidence when examining certain groups of rare diseases to determine how these particular common variants may affect the disease.
According to Omar Mahroo, Professor of Retinal Neuroscience at University College London and Consulting Ophthalmologist at Moorfields Eye Hospital, the future of genomic medicine is driven by systematic bioinformatics analysis of large-scale cohorts of participant data. “The ability to access this data and make these connections between disease symptoms and genetic variation will open countless new perspectives for contemporary disease diagnosis and treatments,” the authors write.
One of the most important goals of EMBL is to gain a molecular understanding of how our genetic makeup interacts with the social, physical and biological elements we are exposed to throughout our lives to affect our health. Learn more about the groundbreaking depth and breadth of future human cohort data and how researchers at EMBL will use them to improve our understanding of human diseases.
📩 09/03/2023 23:36