Sub-cellular level resolution of common genetic variation in the photoreceptor layer identifies continuum between rare disease and common variation.
Photoreceptor cells (PRCs) are the light-detecting cells of the retina. Such cells can be non-invasively imaged using optical coherence tomography (OCT) which is used in clinical settings to diagnose and monitor ocular diseases. Here we present the largest genome-wide association study of PRC morpho...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-02-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010587&type=printable |
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| author | Hannah Currant Tomas W Fitzgerald Praveen J Patel Anthony P Khawaja UK Biobank Eye and Vision Consortium Andrew R Webster Omar A Mahroo Ewan Birney |
| author_facet | Hannah Currant Tomas W Fitzgerald Praveen J Patel Anthony P Khawaja UK Biobank Eye and Vision Consortium Andrew R Webster Omar A Mahroo Ewan Birney |
| author_sort | Hannah Currant |
| collection | DOAJ |
| description | Photoreceptor cells (PRCs) are the light-detecting cells of the retina. Such cells can be non-invasively imaged using optical coherence tomography (OCT) which is used in clinical settings to diagnose and monitor ocular diseases. Here we present the largest genome-wide association study of PRC morphology to date utilising quantitative phenotypes extracted from OCT images within the UK Biobank. We discovered 111 loci associated with the thickness of one or more of the PRC layers, many of which had prior associations to ocular phenotypes and pathologies, and 27 with no prior associations. We further identified 10 genes associated with PRC thickness through gene burden testing using exome data. In both cases there was a significant enrichment for genes involved in rare eye pathologies, in particular retinitis pigmentosa. There was evidence for an interaction effect between common genetic variants, VSX2 involved in eye development and PRPH2 known to be involved in retinal dystrophies. We further identified a number of genetic variants with a differential effect across the macular spatial field. Our results suggest a continuum between common and rare variation which impacts retinal structure, sometimes leading to disease. |
| format | Article |
| id | doaj-art-cea33a204fb344ad9780126c38edef8b |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2023-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-cea33a204fb344ad9780126c38edef8b2025-08-20T03:25:19ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042023-02-01192e101058710.1371/journal.pgen.1010587Sub-cellular level resolution of common genetic variation in the photoreceptor layer identifies continuum between rare disease and common variation.Hannah CurrantTomas W FitzgeraldPraveen J PatelAnthony P KhawajaUK Biobank Eye and Vision ConsortiumAndrew R WebsterOmar A MahrooEwan BirneyPhotoreceptor cells (PRCs) are the light-detecting cells of the retina. Such cells can be non-invasively imaged using optical coherence tomography (OCT) which is used in clinical settings to diagnose and monitor ocular diseases. Here we present the largest genome-wide association study of PRC morphology to date utilising quantitative phenotypes extracted from OCT images within the UK Biobank. We discovered 111 loci associated with the thickness of one or more of the PRC layers, many of which had prior associations to ocular phenotypes and pathologies, and 27 with no prior associations. We further identified 10 genes associated with PRC thickness through gene burden testing using exome data. In both cases there was a significant enrichment for genes involved in rare eye pathologies, in particular retinitis pigmentosa. There was evidence for an interaction effect between common genetic variants, VSX2 involved in eye development and PRPH2 known to be involved in retinal dystrophies. We further identified a number of genetic variants with a differential effect across the macular spatial field. Our results suggest a continuum between common and rare variation which impacts retinal structure, sometimes leading to disease.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010587&type=printable |
| spellingShingle | Hannah Currant Tomas W Fitzgerald Praveen J Patel Anthony P Khawaja UK Biobank Eye and Vision Consortium Andrew R Webster Omar A Mahroo Ewan Birney Sub-cellular level resolution of common genetic variation in the photoreceptor layer identifies continuum between rare disease and common variation. PLoS Genetics |
| title | Sub-cellular level resolution of common genetic variation in the photoreceptor layer identifies continuum between rare disease and common variation. |
| title_full | Sub-cellular level resolution of common genetic variation in the photoreceptor layer identifies continuum between rare disease and common variation. |
| title_fullStr | Sub-cellular level resolution of common genetic variation in the photoreceptor layer identifies continuum between rare disease and common variation. |
| title_full_unstemmed | Sub-cellular level resolution of common genetic variation in the photoreceptor layer identifies continuum between rare disease and common variation. |
| title_short | Sub-cellular level resolution of common genetic variation in the photoreceptor layer identifies continuum between rare disease and common variation. |
| title_sort | sub cellular level resolution of common genetic variation in the photoreceptor layer identifies continuum between rare disease and common variation |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010587&type=printable |
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