Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

Author(s): Hysi PG(1), Cheng CY(2), Springelkamp H(3), Macgregor S(4), Bailey JN(5), Wojciechowski R(6), Vitart V(7), Nag A(8), Hewitt AW(9), Höhn R(10), Venturini C(11), Mirshahi A(10), Ramdas WD(12), Thorleifsson G(13), Vithana E(14), Khor CC(15), Stefansson AB(16), Liao J(17), Haines JL(18), Amin N(19), Wang YX(20), Wild PS(21), Ozel AB(22), Li JZ(22), Fleck BW(23), Zeller T(24), Staffieri SE(9), Teo YY(25), Cuellar-Partida G(26), Luo X(27), Allingham RR(28), Richards JE(29), Senft A(30), Karssen LC(19), Zheng Y(31), Bellenguez C(32),Xu L(20), Iglesias AI(19), Wilson JF(33), Kang JH(34), van Leeuwen EM(19), Jonsson V(35), Thorsteinsdottir U(13), Despriet DD(29), Ennis S(36), Moroi SE(37), Martin NG(38), Jansonius NM(39), Yazar S(40), Tai ES(41), Amouyel P(42), Kirwan J(43), van Koolwijk LM(19), Hauser MA(44), Jonasson F(45), Leo P(46), Loomis SJ(47), Fogarty R(48),Rivadeneira F(49), Kearns L(9), Lackner KJ(50), de Jong PT(51), Simpson CL(52), Pennell CE(53), Oostra BA(54), Uitterlinden AG(49), Saw SM(55), Lotery AJ(56), Bailey-Wilson JE(52), Hofman A(57), Vingerling JR(12), Maubaret C(58), Pfeiffer N(10), Wolfs RC(29), Lemij HG(59), Young TL(27), Pasquale LR(60), Delcourt C5(8), Spector TD(8), Klaver CC(12),Small KS(8), Burdon KP(48), Stefansson K(13), Wong TY(61); BMES GWAS Group; NEIGHBORHOOD Consortium; Wellcome Trust Case Control Consortium (2),Viswanathan A(62), Mackey DA(63), Craig JE(64), Wiggs JL(65), van Duijn CM(66), Hammond CJ(1), Aung T(67)

1 1] Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. [2].
2 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore. [3] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore. [4] Duke-National University of Singapore Graduate Medical School, Singapore. [5].
3 1] Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands. [2] Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. [3].
4 1] Statistical Genetics, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Queensland, Australia. [2].
5 1] Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA. [2].
6 1] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. [2] National Human Genome Research Institute, US National Institutes of Health, Baltimore, Maryland, USA. [3].
7 Medical Research Council (MRC) Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
8 Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
9 Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
10 Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany.
11 1] Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. [2] Institute of Ophthalmology, University College London, London, UK.
12 1] Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands. [2] Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
13 deCODE/Amgen, Reykjavik, Iceland.
14 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore. [3] Duke-National University of Singapore Graduate Medical School, Singapore.
15 1] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore. [2] Division of Human Genetics, Genome Institute of Singapore, Singapore.
16 Eye Clinic, Reykjavik, Iceland.
17 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore.
18 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
19 Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
20 Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China.
21 Department of Internal Medicine II, University Medical Center Mainz, Mainz, Germany.
22 Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
23 National Health Service (NHS) Princess Alexandra Eye Pavilion, Edinburgh, UK.
24 Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.
25 1] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore. [2] Department of Statistics and Applied Probability, National University of Singapore, Singapore.
26 Statistical Genetics, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Queensland, Australia.
27 Duke Eye Center, Duke University, Durham, North Carolina, USA.
28 Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA.
29 Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.
30 Institute of Medical Biometry and Statistics, University Hospital Schleswig-Holstein, Lübeck, Germany.
31 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
32 1] INSERM, UMR 774, Lille, France. [2] Université Lille 2, Lille, France. [3] Institut Pasteur de Lille, Lille, France.
33 Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, UK.
34 Channing Division of Network Medicine, Harvard Medical School, Boston, Massachusetts, USA.
35 Department of Ophthalmology, Landspitali National University Hospital, Reykjavik, Iceland.
36 Human Genetics and Genomic Medicine, Faulty of Medicine, University of Southampton, Southampton, UK.
37 Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.
38 Genetic Epidemiology, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Queensland, Australia.
39 Department of Ophthalmology, University Medical Center Groningen, Groningen, the Netherlands.
40 Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia.
41 1] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore. [2] Duke-National University of Singapore Graduate Medical School, Singapore. [3] Department of Medicine, National University of Singapore and National University Health System, Singapore.
42 1] INSERM, UMR 774, Lille, France. [2] Université Lille 2, Lille, France. [3] Institut Pasteur de Lille, Lille, France. [4] Centre Hospitalier Régional Universitaire de Lille, Lille, France.
43 Department of Ophthalmology, Portsmouth Hospitals NHS Trust, Portsmouth, UK.
44 1] Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA. [2] Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
45 Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
46 The University of Queensland Diamantina Institute, Woollongabba, Queensland, Australia.
47 Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
48 Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
49 1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. [2] Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. [3] Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands.
50 Institute of Clinical Chemistry and Laboratory Medicine, Mainz, Germany.
51 1] Netherlands Institute for Neuroscience, Amsterdam, the Netherlands. [2] Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. [3] Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands.
52 National Human Genome Research Institute, US National Institutes of Health, Baltimore, Maryland, USA.
53 School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.
54 Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
55 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore. [3] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore. [4] Duke-National University of Singapore Graduate Medical School, Singapore.
56 Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
57 1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. [2] Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands.
58 1] Université Bordeaux, ISPED (Institut de Santé Publique, d'Epidémiologie et de Développement), Bordeaux, France. [2] INSERM, Centre INSERM U897 Epidemiologie-Biostatistique Bordeaux, Bordeaux, France.
59 Glaucoma Service, Rotterdam Eye Hospital, Rotterdam, the Netherlands.
60 1] Channing Division of Network Medicine, Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
61 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore. [3] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
62 1] National Institute for Health Research (NIHR) Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and University College London Institute of Ophthalmology, London, UK. [2].
63 1] Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. [2] Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia. [3].
64 1] Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. [2].
65 1] Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA. [2].
66 1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. [2].
67 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. [2] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore. [3].

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 × 10(-11) for rs2472493 near ABCA1 and P = 6.39 × 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 10(-11) for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.

Nat Genet. 2014 Oct;46(10):1126-30. doi: 10.1038/ng.3087. Epub 2014 Aug 31.

PMID: 25173106
http://www.ncbi.nlm.nih.gov/pubmed/25173106

Experimental Paper of the Month manager: Andreas Boehm