Journal article
Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus
Nature genetics, Vol.45(2), pp.155-163
02/2013
DOI: 10.1038/ng.2506
PMCID: PMC3720123
PMID: 23291589
Abstract
Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P< 5 × 10 −8). We further showed that 2 CCT-associated loci, FOXO and FNDC3B , conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4–1.88, P = 2.7 × 10 −10 , and rs4894535 in FNDC3B
had OR = 1.47, 95% CI = 1.29–1.68, P = 4.9 × 10−9). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10 −4 ; tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.
Details
- Title: Subtitle
- Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus
- Creators
- Yi Lu - Queensland Institute of Medical Research, Statistical Genetics, Herston, Brisbane, Queensland, AustraliaVeronique Vitart - Medical Research Council (MRC) Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKKathryn P Burdon - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, AustraliaChiea Chuen Khor - Singapore Eye Research Institute, SingaporeYelena Bykhovskaya - Regenerative Medicine Institute, Ophthalmology Research, Department of Surgery, Cedars-Sinai Medical Center, Division of Surgical Research, Los Angeles, California, USAAlireza Mirshahi - Department of Ophthalmology, University Medical Center Mainz, Mainz, GermanyAlex W Hewitt - Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, AustraliaDemelza Koehn - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, USAPirro G Hysi - Department of Twin Research and Genetic Epidemiology, King’s College London School of Medicine, St Thomas’ Hospital, London, UKWishal D Ramdas - Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The NetherlandsTanja Zeller - University Heart Center Hamburg, Clinic for General and Interventional Cardiology, Hamburg, GermanyEranga N Vithana - Singapore Eye Research Institute, SingaporeBelinda K Cornes - Singapore Eye Research Institute, SingaporeWan-Ting Tay - Singapore Eye Research Institute, SingaporeE Shyong Tai - Saw Swee Hock School of Public Health, National University of Singapore, SingaporeChing-Yu Cheng - Singapore Eye Research Institute, SingaporeJianjun Liu - Saw Swee Hock School of Public Health, National University of Singapore, SingaporeJia-Nee Foo - Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research (ASTAR), SingaporeSeang Mei Saw - Saw Swee Hock School of Public Health, National University of Singapore, SingaporeGudmar Thorleifsson - deCODE genetics, Reykjavik, IcelandKari Stefansson - deCODE genetics, Reykjavik, IcelandDavid P Dimasi - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, AustraliaRichard A Mills - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, AustraliaJenny Mountain - Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Western Australia, AustraliaWei Ang - School of Women’s and Infants’ Health, University of Western Australia, Perth, Western Australia, AustraliaRené Hoehn - Department of Ophthalmology, University Medical Center Mainz, Mainz, GermanyVirginie J M Verhoeven - Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The NetherlandsFranz Grus - Department of Ophthalmology, University Medical Center Mainz, Mainz, GermanyRoger Wolfs - Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The NetherlandsRaphaële Castagne - Institut de Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche de Santé (UMRS) 937, Pierre and Marie Curie University and Medical School, Paris, FranceKarl J Lackner - Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, GermanyHenriët Springelkamp - Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The NetherlandsJian Yang - University of Queensland Diamantina Institute, The University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, AustraliaFridbert Jonasson - Faculty of Medicine, University of Iceland, Reykjavik, IcelandDexter Y L Leung - Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Hong KongLi J Chen - Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Hong KongClement C Y Tham - Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Hong KongIgor Rudan - Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UKZoran Vatavuk - Department of Ophthalmology, Hospital Sestre Milosrdnice, Zagreb, CroatiaCaroline Hayward - Medical Research Council (MRC) Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKJane Gibson - Genetic Epidemiology and Genomic Informatics Group, Human Genetics, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UKAngela J Cree - Clinical Neurosciences Research Grouping, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UKAlex MacLeod - Southampton Eye Unit, Southampton General Hospital, Southampton, UKSarah Ennis - Genetic Epidemiology and Genomic Informatics Group, Human Genetics, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UKOzren Polasek - Croatian Centre for Global Health, University of Split Medical School, Split, CroatiaHarry Campbell - Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UKJames F Wilson - Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UKAnanth C Viswanathan - National Institute for Health Research (NIHR) Biomedical Research Centre, Moorfields Eye Hospital National Health Service (NHS) Foundation Trust and University College London (UCL) Institute of Ophthalmology, London, UKBrian Fleck - Princess Alexandra Eye Pavilion, Edinburgh, UKXiaohui Li - Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USADavid Siscovick - Cardiovascular Health Research Unit, Departments of Medicine, University of Washington, Seattle, Washington, USAKent D Taylor - Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USAJerome I Rotter - Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USASeyhan Yazar - Lions Eye Institute, Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, AustraliaMegan Ulmer - Department of Medicine, Duke University, Durham, North Carolina, USAJun Li - Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USABrian L Yaspan - Vanderbilt University School of Medicine, Center for Human Genetics Research, Nashville, Tennessee, USAAyse B Ozel - Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USAJulia E Richards - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USASayoko E Moroi - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USAJonathan L Haines - Vanderbilt University School of Medicine, Center for Human Genetics Research, Nashville, Tennessee, USAJae H Kang - Brigham and Women’s Hospital, Channing Division of Network Medicine, Boston, Massachusetts, USALouis R Pasquale - Brigham and Women’s Hospital, Channing Division of Network Medicine, Boston, Massachusetts, USAR Rand Allingham - Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USAAllison Ashley-Koch - Department of Medicine, Duke University, Durham, North Carolina, USAPaul Mitchell - Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, AustraliaJie Jin Wang - Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, AustraliaAlan F Wright - Medical Research Council (MRC) Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKCraig Pennell - School of Women’s and Infants’ Health, University of Western Australia, Perth, Western Australia, AustraliaTimothy D Spector - Department of Twin Research and Genetic Epidemiology, King’s College London School of Medicine, St Thomas’ Hospital, London, UKTerri L Young - Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, USACaroline C W Klaver - Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The NetherlandsNicholas G Martin - Queensland Institute of Medical Research, Genetic Epidemiology, Herston, Brisbane, Queensland, AustraliaGrant W Montgomery - Queensland Institute of Medical Research, Molecular Epidemiology, Herston, Brisbane, Queensland, AustraliaMichael G Anderson - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, USATin Aung - Singapore Eye Research Institute, SingaporeColin E Willoughby - Centre for Vision and Vascular Science, Queen’s University Belfast, Belfast, UKJaney L Wiggs - Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USAChi P Pang - Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Hong KongUnnur Thorsteinsdottir - deCODE genetics, Reykjavik, IcelandAndrew J Lotery - Clinical Neurosciences Research Grouping, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UKChristopher J Hammond - Department of Twin Research and Genetic Epidemiology, King’s College London School of Medicine, St Thomas’ Hospital, London, UKCornelia M van Duijn - Department of Epidemiology, Erasmus Medical Center, Rotterdam, The NetherlandsMichael A Hauser - Department of Medicine, Duke University, Durham, North Carolina, USAYaron S Rabinowitz - Regenerative Medicine Institute, Ophthalmology Research, Department of Surgery, Cedars-Sinai Medical Center, Division of Surgical Research, Los Angeles, California, USANorbert Pfeiffer - Department of Ophthalmology, University Medical Center Mainz, Mainz, GermanyDavid A Mackey - Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, AustraliaJamie E Craig - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, AustraliaStuart Macgregor - Queensland Institute of Medical Research, Statistical Genetics, Herston, Brisbane, Queensland, AustraliaTien Y Wong - Saw Swee Hock School of Public Health, National University of Singapore, Singapore
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.45(2), pp.155-163
- DOI
- 10.1038/ng.2506
- PMID
- 23291589
- PMCID
- PMC3720123
- NLM abbreviation
- Nat Genet
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Grant note
- R01 EY018825 || EY / National Eye Institute : NEI F32 EY021436 || EY / National Eye Institute : NEI
- Language
- English
- Date published
- 02/2013
- Academic Unit
- Molecular Physiology and Biophysics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984025670902771
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