Insights into the genetic basis of retinal detachment

UK Biobank Eye & Vision Consortium

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)689–702
Number of pages14
JournalHuman Molecular Genetics
Issue number4
Early online date9 Dec 2019
Publication statusPublished - 15 Feb 2020

Keywords / Materials (for Non-textual outputs)

  • cataract
  • genome
  • myopia
  • retinal detachment.
  • genetics
  • genome-wide association study
  • radiation recall dermatitis
  • self-report
  • biobanks
  • datasets
  • direct-to-consumer genetic testing


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