Insights into the genetic basis of retinal detachment
Author:
Boutin Thibaud S1, Charteris David G2, Chandra Aman34, Campbell Susan1, Hayward Caroline1, Campbell Archie5, Nandakumar Priyanka6, Hinds David6, Mitry Danny7, Vitart Veronique1, , , Agee Michelle, Alipanahi Babak, Auton Adam, Bell Robert K, Bryc Katarzyna, Elson Sarah L, Fontanillas Pierre, Furlotte Nicholas A, Hicks Barry, Huber Karen E, Jewett Ethan M, Jiang Yunxuan, Kleinman Aaron, Lin Keng-Han, Litterman Nadia K, McIntyre Matthew H, McManus Kimberly F, Mountain Joanna L, Noblin Elizabeth S, Northover Carrie A M, Pitts Steven J, Poznik G David, Sathirapongsasuti J Fah, Shelton Janie F, Shringarpure Suyash, Tian Chao, Tung Joyce Y, Vacic Vladimir, Wang Xin, Wilson Catherine H
Affiliation:
1. MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XU Edinburgh, UK 2. Moorfields Eye Hospital, EC1V 2PD London, UK 3. Department of Ophthalmology, Southend University Hospital, Essex SS0 0RY, UK 4. Vision & Eye Research Unit, Anglia Ruskin University, Essex CM1 1SQ, UK 5. Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Institute of Genetics and Molecular Medicine, EH4 2XU Edinburgh, UK 6. 23andMe, Inc. Mountain View, Sunnyvale, CA 94041, USA 7. Department of Ophthalmology, Royal Free NHS Foundation Trust, NW3 2QG London, UK
Abstract
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.
Funder
Health and Disease’ core programme Medical Research Council Royal College of Surgeons Edinburgh Chief Scientist Office Moorfields Eye Hospital Special Trustees Executive Health Department Scottish Funding Council Wellcome Trust medical charity Department of Health Scottish Government Northwest Regional Development Agency Welsh Assembly Government British Heart Foundation and Diabetes UK NIHR Moorfields Eye Charity Fight for Sight Macular Society International Glaucoma Association Alcon Research Institute
Publisher
Oxford University Press (OUP)
Subject
Genetics(clinical),Genetics,Molecular Biology,General Medicine
Cited by
24 articles.
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