| Title: | Insights into the genetic basis of retinal detachment |
| Journal: | Human Molecular Genetics |
| Published: | 9 Dec 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/31816047/ |
| DOI: | https://doi.org/10.1093/hmg/ddz294 |
| URL: | https://academic.oup.com/hmg/article-pdf/29/4/689/32899325/ddz294.pdf |
| Citations: | 29 (11 in last 2 years) as of 8 Aug 2024 |
Publication 5241
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
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.</p>
9 Keywords
- Case-Control Studies
- Cohort Studies
- Genetic Markers
- Genome-Wide Association Study
- Humans
- Meta-Analysis as Topic
- Retinal Detachment
- Sweden
- United Kingdom
41 Authors
- Thibaud S Boutin
- David G Charteris
- Aman Chandra
- Susan Campbell
- Caroline Hayward
- Archie Campbell
- Biobank Eye & Vision Consortium
- Priyanka Nandakumar
- David Hinds
- Michelle Agee
- Babak Alipanahi
- Adam Auton
- Robert K Bell
- Katarzyna Bryc
- Sarah L Elson
- Pierre Fontanillas
- Nicholas A Furlotte
- Barry Hicks
- Karen E Huber
- Ethan M Jewett
- Yunxuan Jiang
- Aaron Kleinman
- Keng-Han Lin
- Nadia K Litterman
- Matthew H McIntyre
- Kimberly F McManus
- Joanna L Mountain
- Elizabeth S Noblin
- Carrie A M Northover
- Steven J Pitts
- G David Poznik
- J Fah Sathirapongsasuti
- Janie F Shelton
- Suyash Shringarpure
- Chao Tian
- Joyce Y Tung
- Vladimir Vacic
- Xin Wang
- Catherine H Wilson
- Danny Mitry
- Veronique Vitart
Enabling scientific discoveries that improve human health