Large-scale study enables new insights into rare eye disorders
EMBL-EBI researchers use UK Biobank data to uncover new information about rare diseases of the eye
Researchers have analysed image and genomic data from the UK Biobank to find insights into rare diseases of the human eye. These include retinal dystrophies – a group of inherited disorders affecting the retina – which are also the leading cause of blindness certification in working-age adults.
The retina is found at the back of the eye. It’s a layered tissue that receives light and converts it into a signal that can be interpreted by the brain. Each retinal layer comprises different cell types that play a unique role in this light conversion process.
For this study published in the journal PLOS Genetics, the researchers focused on photoreceptor cells (PRCs), which are light-detecting cells found in the retina. These cells can be non-invasively imaged using optical coherence tomography (OCT), a service now commonly offered in many opticians. Using OCT image data and genomic data stored in the UK Biobank, researchers were able to generate the largest genome-wide association study of PRCs.
Detecting photoreceptor cells (PRCs) using optical coherence tomography (OCT)
Optical coherence tomography is used in the clinic to generate images of the retina. It produces an image comparable to an ultrasound scan that can be used to identify the different layers of the retina. The photoreceptor cells are found towards the back of the eye within the retina, comprising three different layers: the outer nuclear layer (ONL), the inner segment (IS) and the outer segment (OS). Changes in the morphology and thickness of these layers are associated with disorders of the retina known collectively as retinal dystrophies.
Rare retinal dystrophies
Rare diseases of the retina are frequently caused by inherited mutations in genes expressed by PRCs. These mutations cause the retina to function incorrectly, resulting in sight impairment or even blindness. Although these individual diseases are rare, together they are the leading cause of blindness in working-age adults.
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 aid the diagnosis of eye disorders. For this study, the researchers used OCT images and the corresponding genomic and medical information of over 30,000 participants stored in the UK Biobank.
The researchers conducted genome-wide association studies (GWAS) on the UK Biobank data to look for genetic variations linked to differences in the thickness of the PRC layers. This led them to identify genomic variations associated with the thickness of one or more of the PRC layers, including those with prior associations with known eye diseases. The newly identified genomic associations are stored and can be openly accessed through the GWAS Catalog.
Some of these genetic variants were known to be linked to eye diseases, but surprisingly, a number of relatively common genetic variants were near genes known to cause rare genetic eye diseases when disrupted. In one case, the researchers were able to explore how combinations of common variants near genes known to be involved in rare eye diseases change the structure of the retina. This gives more confidence when looking into specific rare disease collections to see how these specific common variants might impact disease.