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Hum Mol Genet. 2019 Dec 9. pii: ddz294. doi: 10.1093/hmg/ddz294. [Epub ahead of print]

Insights into the genetic basis of retinal detachment.

Author information

MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XU, Edinburgh, UK.
Moorfields Eye Hospital, EC1V 2PD, London, UK.
Department of Ophthalmology, Southend University Hospital, Essex, SS0 0RY, UK.
Vision & Eye Research Unit, Anglia Ruskin University, Essex, CM1 1SQ, UK.
Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Institute of Genetics and Molecular Medicine, EH4 2XU, Edinburgh, UK.
23andMe, Inc. Mountain View, CA 94041, USA.
Department of Ophthalmology, Royal Free NHS Foundation Trust, NW3 2QG, London, UK.


Retinal detachment 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 dataset, where retinal detachment was ascertained by self-report or hospital records, genetic correlations between retinal detachment 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 retinal detachment cases (N=3977) and two cohorts, each comprising ~1000 clinically-ascertained rhegmatogenous retinal detachment 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 dataset, where retinal detachment is self-reported by participants, firmly establishes six retinal detachment 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 retinal detachment, while the last four point to shared aetiologies with macular condition, myopia and glaucoma. Fine-mapping prioritised 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 retinal detachment aetiology and underlying pathological pathways.


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