title: Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process.
abstract: Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.
authors.affiliation: 1] Department of Ophthalmology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [2] Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Henriët
authors.initials: H
authors.lastname: Springelkamp
authors.affiliation: Department of Ophthalmology, University Medical Center Mainz, Mainz 55131, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Höhn
authors.affiliation: Department of Genetics and Computational Biology, Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Queensland 4006, Australia.
authors.forename: Aniket
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London WC2R 2LS, UK.
authors.forename: Pirro G
authors.initials: PG
authors.lastname: Hysi
authors.affiliation: 1] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119077, Singapore [2] Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Loomis
authors.affiliation: 1] Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA [2] Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Jessica N Cooke
authors.initials: JN
authors.lastname: Bailey
authors.affiliation: Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Gibson
authors.affiliation: deCODE/Amgen, Reykjavik 101, Iceland.
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.affiliation: Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam 1105 BA, the Netherlands.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Janssen
authors.affiliation: Department of Ophthalmology, Duke University Eye Center, Durham, North Carolina 27710, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Wishal D
authors.initials: WD
authors.lastname: Ramdas
authors.affiliation: 1] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119077, Singapore [2] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore [3] Duke-National University of Singapore, Graduate Medical School, Singapore 169857, Singapore.
authors.forename: Eranga
authors.initials: E
authors.lastname: Vithana
authors.affiliation: 1] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119077, Singapore [2] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore.
authors.forename: Monisha E
authors.initials: ME
authors.lastname: Nongpiur
authors.affiliation: Department of Genetics and Computational Biology, Molecular Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Queensland 4006, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: 1] Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China [2] Beijing Ophthalmology and Visual Science Key Lab, Beijing 100730, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Telethon Institute for Child Health Research, Subiaco, Western Australia 6008, Australia.
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Mountain
authors.affiliation: Department of Genetics and Computational Biology, Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Queensland 4006, Australia.
authors.forename: Puya
authors.initials: P
authors.lastname: Gharahkhani
authors.affiliation: Department of Genetics and Computational Biology, Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Queensland 4006, Australia.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Najaf
authors.initials: N
authors.lastname: Amin
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Lennart C
authors.initials: LC
authors.lastname: Karssen
authors.affiliation: Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Kar-Seng
authors.initials: KS
authors.lastname: Sim
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: van Leeuwen
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Adriana I
authors.initials: AI
authors.lastname: Iglesias
authors.affiliation: 1] Department of Ophthalmology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [2] Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Virginie J M
authors.initials: VJ
authors.lastname: Verhoeven
authors.affiliation: Departments of Medicine and Ophthalmology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
authors.affiliation: Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119077, Singapore.
authors.forename: Seng-Chee
authors.initials: SC
authors.lastname: Loon
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Dominiek D G
authors.initials: DD
authors.lastname: Despriet
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London WC2R 2LS, UK.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Nag
authors.affiliation: 1] Department of Twin Research and Genetic Epidemiology, King's College London, London WC2R 2LS, UK [2] UCL Institute of Ophthalmology, London EC1V 9EL, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Venturini
authors.affiliation: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Sanfilippo
authors.affiliation: Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck 23562, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Schillert
authors.affiliation: Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Jae H
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Ophthalmology, Flinders University, Adelaide, South Australia 5042, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Landers
authors.affiliation: 1] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland [2] Department of Ophthalmology, Landspitali National University Hospital, Reykjavik 101, Iceland.
authors.forename: Fridbert
authors.initials: F
authors.lastname: Jonasson
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Cree
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Leonieke M E
authors.initials: LM
authors.lastname: van Koolwijk
authors.affiliation: 1] Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [2] Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [3] Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague 2593 CE, The Netherlands.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.affiliation: Department of Ophthalmology, Flinders University, Adelaide, South Australia 5042, Australia.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Souzeau
authors.affiliation: Department of Ophthalmology, Landspitali National University Hospital, Reykjavik 101, Iceland.
authors.forename: Vesteinn
authors.initials: V
authors.lastname: Jonsson
authors.affiliation: Department of Ophthalmology, Frimley Park Hospital NHS Foundation Trust, Frimley GU16 7UJ, UK.
authors.forename: Geeta
authors.initials: G
authors.lastname: Menon
authors.affiliation: Department of Ophthalmology and Hamilton Glaucoma Center, University of California, San Diego, California 92093, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Weinreb
authors.affiliation: 1] Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [2] Department of Retinal Signal Processing, Netherlands Institute for Neuroscience, Amsterdam 1105 BA, The Netherlands [3] Department of Ophthalmology, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands [4] Department of Ophthalmology, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.affiliation: 1] Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [2] Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [3] Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague 2593 CE, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: 1] Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [2] Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague 2593 CE, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ennis
authors.affiliation: 1] deCODE/Amgen, Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.affiliation: Department of Ophthalmology, Flinders University, Adelaide, South Australia 5042, Australia.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London WC2R 2LS, UK.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Ophthalmology, University Medical Center Mainz, Mainz 55131, Germany.
authors.forename: Alireza
authors.initials: A
authors.lastname: Mirshahi
authors.affiliation: 1] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119077, Singapore [2] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore [3] Duke-National University of Singapore, Graduate Medical School, Singapore 169857, Singapore [4] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore.
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
authors.affiliation: 1] Department of Ophthalmology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [2] Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.affiliation: 1] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore [2] Department of Statistics and Applied Probability, National University of Singapore, Singapore 119077, Singapore.
authors.forename: Yik-Ying
authors.initials: YY
authors.lastname: Teo
authors.affiliation: 1] Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA [2] Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Roger C W
authors.initials: RC
authors.lastname: Wolfs
authors.affiliation: Glaucoma Service, The Rotterdam Eye Hospital, Rotterdam 3011 BH, The Netherlands.
authors.forename: Hans G
authors.initials: HG
authors.lastname: Lemij
authors.affiliation: 1] Duke-National University of Singapore, Graduate Medical School, Singapore 169857, Singapore [2] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore [3] Department of Medicine, National University of Singapore and National University Health System, Singapore 119077, Singapore.
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.affiliation: Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, The Netherlands.
authors.forename: Nomdo M
authors.initials: NM
authors.lastname: Jansonius
authors.affiliation: 1] Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China [2] Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Seegartenklinik Heidelberg, Heidelberg 69117, Germany.
authors.forename: Jost B
authors.initials: JB
authors.lastname: Jonas
authors.affiliation: 1] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119077, Singapore [2] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore [3] Duke-National University of Singapore, Graduate Medical School, Singapore 169857, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: 1] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119077, Singapore [2] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore.
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.affiliation: NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 2PD, UK.
authors.forename: Ananth C
authors.initials: AC
authors.lastname: Viswanathan
authors.affiliation: 1] Department of Ophthalmology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands [2] Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.affiliation: Department of Ophthalmology, Flinders University, Adelaide, South Australia 5042, Australia.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
authors.affiliation: Department of Genetics and Computational Biology, Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Queensland 4006, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Macgregor
authors.affiliation: 1] Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia [2] Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia 6009, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lotery
authors.affiliation: 1] deCODE/Amgen, Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.affiliation: 1] Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam 1105 BA, the Netherlands [2] Department of Ophthalmology, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands [3] Department of Clinical Genetics, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands.
authors.forename: Arthur A B
authors.initials: AA
authors.lastname: Bergen
authors.affiliation: Department of Ophthalmology, Duke University Eye Center, Durham, North Carolina 27710, USA.
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
authors.affiliation: Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA.
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
authors.affiliation: Department of Ophthalmology, University Medical Center Mainz, Mainz 55131, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Pfeiffer
authors.affiliation: 1] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119077, Singapore [2] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore [3] Duke-National University of Singapore, Graduate Medical School, Singapore 169857, Singapore.
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: 1] Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA [2] Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Louis R
authors.initials: LR
authors.lastname: Pasquale
authors.affiliation: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia.
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London WC2R 2LS, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hammond
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D005901:Glaucoma / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D009898:Optic Disk / Q000473:pathology; D009900:Optic Nerve / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics