Large-scale study enables new insights into rare eye disorders – ScienceDaily

The researchers analyzed image and genome data from the UK Biobank to find insights into rare diseases affecting the human eye. This includes retinal dystrophies – a group of genetic disorders that affect the retina – which is also the leading cause of blindness certification in adults of working age.

The retina is found at the back of the eye. It is a layered tissue that receives light and converts it into a signal that the brain can interpret. Each retinal layer is made up of different cell types that play a unique role in this light conversion process.

For this study published in the journal PLOS GeneticsThe researchers focused on photoreceptor cells (PRCs), which are light-detecting cells found in the retina. These cells can be imaged non-invasively using optical coherence tomography (OCT), a service now commonly offered by many optometrists. Using OCT image data and genetic data stored in the UK Biobank, the researchers were able to create the largest genome-wide associational study of PRCs.

Rare retinal atrophy

Rare diseases of the retina are often caused by inherited mutations in genes expressed by CSCs. These mutations cause the retina to function incorrectly, resulting in poor eyesight or even blindness. Although rare, these individual diseases are collectively the leading cause of blindness in adults of working age.

“We had access to paired images and genotype data on a scale not seen in a study of this type,” said Hannah Courant, a former EMBL-EBI doctoral student and postdoctoral fellow at Novo Nordisk. Foundation Center for Protein Research (CPR) University of Copenhagen. “Access to this large amount of data was critical to the study and enabled us to identify genetic links to rare retinal atrophy. This work has identified new avenues of research and raised new questions about rare retinal atrophy.”

Link genotype and phenotype

OCT produces high-resolution images that can be used to identify the different layers and structures within the retina. These images are commonly used in the clinic to help diagnose eye disorders. In this study, the researchers used OCT images and corresponding genetic and medical information from more than 30,000 participants stored in the UK Biobank.

“The UK biobank is a rich and invaluable resource with huge potential to enable genomic medicine,” said Ewan Birney, Deputy Director General of the European Molecular Biology Laboratory (EMBL). “There is a lot of potential waiting for the data stored there to be released, allowing us to understand human biology and how and when disease goes wrong.”

Genomic Medicine Leadership

The researchers conducted genome-wide association studies (GWAS) on UK biobank data to look for genetic differences associated with differences in the thickness of the PRC strata. This led them to identify genetic variations associated with the thickness of one or more PRC layers, including those with prior associations with known eye diseases. Newly identified genomic associations are stored and openly accessible through the GWAS catalog.

Some of these genetic variants were known to be associated with eye diseases, but surprisingly, a number of relatively common genetic variants were close to genes known to cause genetic eye diseases when malfunctioning. In one case, the researchers were able to explore how clusters of common variants near genes known to be involved in rare eye diseases alter the structure of the retina. This gives more confidence when looking at specific groups of rare diseases to see how these specific common variants may affect disease.

“Systematic analysis of bioinformatics of large-scale participant data cohorts is driving the future of genomic medicine,” said Omar Mahro, professor of retinal neuroscience at University College London and consultant ophthalmologist at Moorfields Eye Hospital. “Access to this data and the ability to make these connections between disease phenotypes and genetic variation will open many new opportunities for disease diagnosis and novel therapies.”

Developing a molecular understanding of how the human ecosystem – the social, physical and biological factors to which we are exposed throughout our lives – interacts with our genetic makeup to influence our health is a priority for EMBL. Find out more about how researchers across EMBL are leveraging the unprecedented depth and breadth of emerging human cohort data to aid our understanding of human disease.

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