机构:[1]School of Optometry & Vision Sciences, Cardiff University, Cardiff, UK[2]Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, USA[3]Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore[4]Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore[5]Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands[6]Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands[7]Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK[8]NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK[9]Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore[10]Institute of Genetics and Molecular Medicine, Medical Research Council Human Genetics Unit, University of Edinburgh, Edinburgh, UK[11]Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia[12]Department of Ophthalmology, King's College London, London, UK[13]Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia[14]Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Australia[15]Beijing Institute of Ophthalmology, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University,Beijing, China研究所眼科研究所首都医科大学附属北京同仁医院首都医科大学附属同仁医院[16]Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Mainz, Germany[17]Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany[18]Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany[19]Department of Ophthalmology, Central Hospital of Central Finland, Jyväskylä, Finland[20]Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Finland[21]Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland[22]Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland[23]Department of Public Health, University of Helsinki, Helsinki, Finland[24]Institute of Molecular Genetics, National Research Council of Italy, Pavia, Italy[25]Institute for Maternal and Child Health - IRCCS ‘Burlo Garofolo’, Trieste, Italy[26]Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands[27]Department of Pediatrics Erasmus Medical Center, Rotterdam, the Netherlands[28]Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore[29]Department of Ophthalmology, National University Hospital, Singapore[30]Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA[31]Department of Ophthalmology, Medical Faculty Mannheim of the University Heidelberg, Mannheim, Germany[32]Department of Ophthalmology, Western Sydney Local Health District, Sydney, Australia[33]Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia[34]Department of Ophthalmology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland[35]Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore[36]Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore[37]Department of Statistics and Applied Probability, National University of Singapore, Singapore[38]Division of Human Genetics, Genome Institute of Singapore, Singapore[39]School of Social and Community Medicine, University of Bristol, Bristol, UK[40]Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands
出处:
ISSN:
摘要:
Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI: 1.08-1.16), p=5.55x10(-9). No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.
基金:
UK Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC); Wellcome TrustWellcome TrustEuropean Commission [102215/2/13/2]; University of Bristol; NIHR Senior Research Fellowship [SRF-2015-08-005]; Wellcome Trust ISSF Populations Pilot Award [508353/509506]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81770890]; National Health and Medical Research Council of Australia (NHMRC) Senior Research FellowshipNational Health and Medical Research Council of Australia [1138585]; Victorian Government; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [G1000143]; Cancer Research UKCancer Research UK [C864/A14136]; Research into Aging [262]; ENGAGE (FP7-HEALTH-F4) [201, 413]; European Union through the GENOMEUTWIN project [QLG2-CT-2002-01254]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Academy of Finland Aging Programme; Finnish Ministry of Culture and Education; University of Jyvaskyla; Silmasaatio Foundation; Evald & Hilda Nissi Foundation; Erasmus Medical Centre, Rotterdam; Netherlands Organisation for Scientific Research (NWO)Netherlands Organization for Scientific Research (NWO); Netherlands Organisation for Health Research and Development (ZonMw)Netherlands Organization for Health Research and Development; Dutch Ministry of Education, Culture and Science; Dutch Ministry of Health, Welfare, and Sports; European Commission (DG XII)European CommissionEuropean Commission Joint Research Centre; UitZicht [2013-24]; Gutenberg Health Study [AZ 961-386261/733]; Johannes Gutenberg-University of Mainz; National Genome Network "NGFNplus", Federal Ministry of Education and Research, Germany [A301GS0833]; Italian Ministry of Education, University and Research (MIUR)Ministry of Education, Universities and Research (MIUR) [5571/DSPAR/2002]; University of Western Australia (UWA); Telethon Institute for Child Health Research; Raine Medical Research Foundation; UWA Faculty of Medicine, Dentistry and Health Sciences; Women's and Infant's Research Foundation; Curtin University; Australian National Health and Medical Research Council (NHMRC) projectNational Health and Medical Research Council of Australia [1021105]; LEI; Australian Foundation for the Prevention of Blindness; ORIA; NHMRC CJ Martin Early Career FellowshipNational Health and Medical Research Council of Australia [1111437]; Dutch governmental Innovational Research Incentives Scheme Grant [VICI 91815655]; Horizon ERC Consolidator Grant [648268]; Erasmus Medical Center; Erasmus University, Rotterdam, The NetherlandsNetherlands Government; Netherlands Organization for Health Research and Development (ZonMw)Netherlands Organization for Health Research and Development; UitZicht; Research Institute for Diseases in the Elderly; Ministry of Education, Culture and ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Ministry for Health, Welfare and Sports; Municipality of Rotterdam; Netherlands Genomics Initiative/NWONetherlands Organization for Scientific Research (NWO); Center for Medical Systems Biology of NGI; Lijf en Leven; Henkes Stichting; Landelijke Stichting voor Blinden en Slechtzienden; Oogfonds; MaculaFonds; National Medical Research Council (NMRC), SingaporeNational Medical Research Council, Singapore [0796/2003, 1176/2008, 1149/2008, STaR/0003/2008, 1249/2010, CG/SERI/2010, CIRG/1371/2013, CIRG/1417/2015]; Biomedical Research Council, SingaporeAgency for Science Technology & Research (ASTAR) [08/1/35/19/550, 09/1/35/19/616]; NMRCNational Medical Research Council, Singapore [CSA/033/2012]; Biomedical Research Council (BMRC)Agency for Science Technology & Research (ASTAR) [06/1/21/19/466]; Wellcome TrustWellcome TrustEuropean Commission; European Community's Seventh Framework Programme (FP7)European Commission; National Institute for Health Research Clinical Research Facility at Guy's and St. Thomas' National Health Service Foundation Trust; National Institute for Health Research Biomedical Research Centre at Guy's and St. Thomas' National Health Service Foundation Trust and King's College London; Intramural Research Program of the National Human Genome Research Institute, National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI); Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [G9815508, MC_PC_15018, MR/K023721/1] Funding Source: researchfish; NATIONAL HUMAN GENOME RESEARCH INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [ZIAHG200327] Funding Source: NIH RePORTER; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MR/K023721/1] Funding Source: UKRI
第一作者机构:[1]School of Optometry & Vision Sciences, Cardiff University, Cardiff, UK
共同第一作者:
通讯作者:
通讯机构:[1]School of Optometry & Vision Sciences, Cardiff University, Cardiff, UK[*1]School of Optometry & Vision Sciences, Cardiff University, Maindy Road, Cardiff, CF24 4HQ, UK
推荐引用方式(GB/T 7714):
Shah Rupal L.,Li Qing,Zhao Wanting,et al.A genome-wide association study of corneal astigmatism: The CREAM Consortium[J].MOLECULAR VISION.2018,24:127-142.
APA:
Shah, Rupal L.,Li, Qing,Zhao, Wanting,Tedja, Milly S.,Tideman, J. Willem L....&Bailey-Wilson, Joan E..(2018).A genome-wide association study of corneal astigmatism: The CREAM Consortium.MOLECULAR VISION,24,
MLA:
Shah, Rupal L.,et al."A genome-wide association study of corneal astigmatism: The CREAM Consortium".MOLECULAR VISION 24.(2018):127-142