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Insights into the genetic basis of retinal detachment
Retinal detachment (RD) is a serious and common condition, but genetic studies to date have been hampered by the small size of the assembled cohorts. In the UK Biobank data set, where RD was ascertained by self-report or hospital records, genetic correlations between RD and high myopia or cataract o...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068119/ https://www.ncbi.nlm.nih.gov/pubmed/31816047 http://dx.doi.org/10.1093/hmg/ddz294 |
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author | Boutin, Thibaud S Charteris, David G Chandra, Aman Campbell, Susan Hayward, Caroline Campbell, Archie Nandakumar, Priyanka Hinds, David Mitry, Danny Vitart, Veronique |
author_facet | Boutin, Thibaud S Charteris, David G Chandra, Aman Campbell, Susan Hayward, Caroline Campbell, Archie Nandakumar, Priyanka Hinds, David Mitry, Danny Vitart, Veronique |
author_sort | Boutin, Thibaud S |
collection | PubMed |
description | Retinal detachment (RD) is a serious and common condition, but genetic studies to date have been hampered by the small size of the assembled cohorts. In the UK Biobank data set, where RD was ascertained by self-report or hospital records, genetic correlations between RD and high myopia or cataract operation were, respectively, 0.46 (SE = 0.08) and 0.44 (SE = 0.07). These correlations are consistent with known epidemiological associations. Through meta-analysis of genome-wide association studies using UK Biobank RD cases (N = 3 977) and two cohorts, each comprising ~1 000 clinically ascertained rhegmatogenous RD patients, we uncovered 11 genome-wide significant association signals. These are near or within ZC3H11B, BMP3, COL22A1, DLG5, PLCE1, EFEMP2, TYR, FAT3, TRIM29, COL2A1 and LOXL1. Replication in the 23andMe data set, where RD is self-reported by participants, firmly establishes six RD risk loci: FAT3, COL22A1, TYR, BMP3, ZC3H11B and PLCE1. Based on the genetic associations with eye traits described to date, the first two specifically impact risk of a RD, whereas the last four point to shared aetiologies with macular condition, myopia and glaucoma. Fine-mapping prioritized the lead common missense variant (TYR S192Y) as causal variant at the TYR locus and a small set of credible causal variants at the FAT3 locus. The larger study size presented here, enabled by resources linked to health records or self-report, provides novel insights into RD aetiology and underlying pathological pathways. |
format | Online Article Text |
id | pubmed-7068119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-70681192020-03-18 Insights into the genetic basis of retinal detachment Boutin, Thibaud S Charteris, David G Chandra, Aman Campbell, Susan Hayward, Caroline Campbell, Archie Nandakumar, Priyanka Hinds, David Mitry, Danny Vitart, Veronique Hum Mol Genet Association Studies Article Retinal detachment (RD) is a serious and common condition, but genetic studies to date have been hampered by the small size of the assembled cohorts. In the UK Biobank data set, where RD was ascertained by self-report or hospital records, genetic correlations between RD and high myopia or cataract operation were, respectively, 0.46 (SE = 0.08) and 0.44 (SE = 0.07). These correlations are consistent with known epidemiological associations. Through meta-analysis of genome-wide association studies using UK Biobank RD cases (N = 3 977) and two cohorts, each comprising ~1 000 clinically ascertained rhegmatogenous RD patients, we uncovered 11 genome-wide significant association signals. These are near or within ZC3H11B, BMP3, COL22A1, DLG5, PLCE1, EFEMP2, TYR, FAT3, TRIM29, COL2A1 and LOXL1. Replication in the 23andMe data set, where RD is self-reported by participants, firmly establishes six RD risk loci: FAT3, COL22A1, TYR, BMP3, ZC3H11B and PLCE1. Based on the genetic associations with eye traits described to date, the first two specifically impact risk of a RD, whereas the last four point to shared aetiologies with macular condition, myopia and glaucoma. Fine-mapping prioritized the lead common missense variant (TYR S192Y) as causal variant at the TYR locus and a small set of credible causal variants at the FAT3 locus. The larger study size presented here, enabled by resources linked to health records or self-report, provides novel insights into RD aetiology and underlying pathological pathways. Oxford University Press 2020-03-13 2019-12-09 /pmc/articles/PMC7068119/ /pubmed/31816047 http://dx.doi.org/10.1093/hmg/ddz294 Text en © The Author(s) 2019. Published by Oxford University Press. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Association Studies Article Boutin, Thibaud S Charteris, David G Chandra, Aman Campbell, Susan Hayward, Caroline Campbell, Archie Nandakumar, Priyanka Hinds, David Mitry, Danny Vitart, Veronique Insights into the genetic basis of retinal detachment |
title | Insights into the genetic basis of retinal detachment |
title_full | Insights into the genetic basis of retinal detachment |
title_fullStr | Insights into the genetic basis of retinal detachment |
title_full_unstemmed | Insights into the genetic basis of retinal detachment |
title_short | Insights into the genetic basis of retinal detachment |
title_sort | insights into the genetic basis of retinal detachment |
topic | Association Studies Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068119/ https://www.ncbi.nlm.nih.gov/pubmed/31816047 http://dx.doi.org/10.1093/hmg/ddz294 |
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