Insights into the genetic basis of retinal detachment.
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
13 03 2020
13 03 2020
Historique:
received:
05
07
2019
revised:
29
11
2019
accepted:
05
12
2019
pubmed:
10
12
2019
medline:
4
6
2021
entrez:
10
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31816047
pii: 5670499
doi: 10.1093/hmg/ddz294
pmc: PMC7068119
doi:
Substances chimiques
Genetic Markers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
689-702Subventions
Organisme : Medical Research Council
ID : MC_PC_12028
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : CZD/16/6
Pays : United Kingdom
Organisme : British Heart Foundation
Pays : United Kingdom
Organisme : Department of Health
ID : BRC3_026
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : CZB/4/705
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Investigateurs
Michelle Agee
(M)
Babak Alipanahi
(B)
Adam Auton
(A)
Robert K Bell
(RK)
Katarzyna Bryc
(K)
Sarah L Elson
(SL)
Pierre Fontanillas
(P)
Nicholas A Furlotte
(NA)
Barry Hicks
(B)
Karen E Huber
(KE)
Ethan M Jewett
(EM)
Yunxuan Jiang
(Y)
Aaron Kleinman
(A)
Keng-Han Lin
(KH)
Nadia K Litterman
(NK)
Matthew H McIntyre
(MH)
Kimberly F McManus
(KF)
Joanna L Mountain
(JL)
Elizabeth S Noblin
(ES)
Carrie A M Northover
(CAM)
Steven J Pitts
(SJ)
G David Poznik
(GD)
J Fah Sathirapongsasuti
(JF)
Janie F Shelton
(JF)
Suyash Shringarpure
(S)
Chao Tian
(C)
Joyce Y Tung
(JY)
Vladimir Vacic
(V)
Xin Wang
(X)
Catherine H Wilson
(CH)
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press.
Références
JAMA Ophthalmol. 2016 Jul 1;134(7):794-801
pubmed: 27197004
Invest Ophthalmol Vis Sci. 2011 Apr 20;52(5):2551-5
pubmed: 21245406
Bioinformatics. 2016 Oct 15;32(20):3207-3209
pubmed: 27318201
Nat Genet. 2018 Nov;50(11):1505-1513
pubmed: 30297969
Development. 2013 Nov;140(22):4602-13
pubmed: 24131632
Nat Commun. 2018 Jun 11;9(1):2278
pubmed: 29891935
Trans Am Ophthalmol Soc. 1989;87:143-55; discussion 155-7
pubmed: 2562517
Ophthalmol Clin North Am. 2001 Dec;14(4):695-704
pubmed: 11787748
Arch Ophthalmol. 2005 Sep;123(9):1237-41
pubmed: 16157805
Development. 2016 Jun 15;143(12):2172-82
pubmed: 27122175
Bioinformatics. 2016 May 15;32(10):1493-501
pubmed: 26773131
Ageing Res Rev. 2015 May;21:71-7
pubmed: 25841656
Am J Hum Genet. 2011 Mar 11;88(3):294-305
pubmed: 21376301
Nat Genet. 2015 Mar;47(3):284-90
pubmed: 25642633
PLoS Comput Biol. 2015 Apr 17;11(4):e1004219
pubmed: 25885710
Dtsch Arztebl Int. 2014 Jan 6;111(1-2):12-21; quiz 22
pubmed: 24565273
Br J Ophthalmol. 2010 Jun;94(6):678-84
pubmed: 19515646
Clin Ophthalmol. 2018 Apr 05;12:651-656
pubmed: 29670325
J Comp Neurol. 2016 Dec 15;524(18):3696-3716
pubmed: 27097562
Am J Hum Genet. 2013 Aug 8;93(2):264-77
pubmed: 24144296
Nat Genet. 2018 Jun;50(6):834-848
pubmed: 29808027
Am J Ophthalmol. 1999 Oct;128(4):472-6
pubmed: 10577588
Ophthalmic Res. 2000 Sep-Oct;32(5):237-9
pubmed: 10971186
Eye (Lond). 2014 Feb;28(2):113-7
pubmed: 24113300
Ophthalmology. 2015 Nov;122(11):2179-85
pubmed: 26278859
PLoS Genet. 2013 Apr;9(4):e1003442
pubmed: 23593034
Surv Ophthalmol. 1979 Jan-Feb;23(4):213-48
pubmed: 424991
Ophthalmic Genet. 2016 Jun;37(2):121-9
pubmed: 26757352
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
Nat Genet. 2015 Nov;47(11):1236-41
pubmed: 26414676
Nat Genet. 2018 Jul;50(7):906-908
pubmed: 29892013
Eye (Lond). 2008 Oct;22(10):1233-42
pubmed: 18309337
Nat Genet. 2001 Nov;29(3):306-9
pubmed: 11600885
Ophthalmology. 2011 Jul;118(7):1429-34
pubmed: 21561662
PLoS Genet. 2013;9(2):e1003299
pubmed: 23468642
Nat Commun. 2018 Jun 29;9(1):2537
pubmed: 29959328
Hum Genet. 2003 Apr;112(4):387-99
pubmed: 12579416
PLoS Genet. 2010 Jun 24;6(6):e1000993
pubmed: 20585627
Hum Mol Genet. 2013 Aug 1;22(15):3174-85
pubmed: 23585552
Nat Commun. 2014 Sep 22;5:4883
pubmed: 25241763
Acta Ophthalmol (Copenh). 1987 Apr;65(2):213-22
pubmed: 3604613
Ophthalmic Physiol Opt. 2005 Sep;25(5):381-91
pubmed: 16101943
Bioinformatics. 2014 Oct;30(19):2811-2
pubmed: 24930139
Nat Genet. 2018 Apr;50(4):549-558
pubmed: 29559693
PLoS One. 2018 Jul 26;13(7):e0200785
pubmed: 30048462
Nat Genet. 2007 Dec;39(12):1443-52
pubmed: 17952075
Mamm Genome. 2004 Oct;15(10):749-58
pubmed: 15520878
Am J Hum Genet. 2011 Jan 7;88(1):76-82
pubmed: 21167468
Ophthalmology. 2016 May;123(5):1036-42
pubmed: 26875007
Nat Commun. 2017 Dec 13;8(1):2108
pubmed: 29235454
Nat Commun. 2017 Nov 28;8(1):1826
pubmed: 29184056
Invest Ophthalmol Vis Sci. 2010 Oct;51(10):4963-8
pubmed: 20554615
Hum Mol Genet. 2019 Apr 1;28(7):1162-1172
pubmed: 30535121
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
Genes Dev. 2006 May 15;20(10):1308-20
pubmed: 16702404
Biometrics. 1999 Dec;55(4):997-1004
pubmed: 11315092
Graefes Arch Clin Exp Ophthalmol. 1999 Feb;237(2):137-44
pubmed: 9987630
Am J Hum Genet. 2007 Aug;81(2):208-27
pubmed: 17668372
Nat Genet. 2018 Jun;50(6):778-782
pubmed: 29785010
Nat Genet. 2014 Mar;46(3):310-5
pubmed: 24487276
Genet Epidemiol. 2013 Sep;37(6):539-50
pubmed: 23788246
J Biol Chem. 2004 May 21;279(21):22514-21
pubmed: 15016833
Hum Mutat. 2016 Oct;37(10):1085-96
pubmed: 27406592
Arch Ophthalmol. 1977 Mar;95(3):418-22
pubmed: 843271
Invest Ophthalmol Vis Sci. 2003 Sep;44(9):4035-43
pubmed: 12939326
PLoS Med. 2015 Mar 31;12(3):e1001779
pubmed: 25826379
Ophthalmologica. 2016;235(1):57-60
pubmed: 26485405
Retina. 2005 Jun;25(4):473-8
pubmed: 15933595
Ophthalmology. 2013 Mar;120(3):616-622
pubmed: 23218185
Invest Ophthalmol Vis Sci. 2005 Feb;46(2):663-8
pubmed: 15671297
Nat Genet. 2017 Sep;49(9):1311-1318
pubmed: 28759005