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Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

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机构: [1]Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands [2]Department of Epidemiology, Erasmus Medical Center, Rotterdam,The Netherlands [3]Department of Twin Research and Genetic Epidemiology, King’s College London School of Medicine, London, UK [4]Inherited Disease ResearchBranch, National Human Genome Research Institute, US National Institutes of Health, Baltimore, Maryland, USA [5]Department of Epidemiology, Johns HopkinsBloomberg School of Public Health, Baltimore, Maryland, USA [6]Saw Swee Hock School of Public Health, National University Health Systems, National University ofSingapore, Singapore [7]Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Hong Kong [8]Department of Ophthalmology, UniversityMedical Center Mainz, Mainz, Germany [9]Department of Statistical Genetics, Queensland Institute of Medical Research, Herston, Brisbane, Queensland, Australia [10]Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia [11]Centre for Ophthalmologyand Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia [12]Department of Ophthalmology, National University HealthSystems, National University of Singapore, Singapore [13]Singapore Eye Research Institute, Singapore National Eye Centre, Singapore [14]Medical Research CouncilCentre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK [15]School of Social andCommunity Medicine, University of Bristol, Bristol, UK [16]Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere,Tampere, Finland [17]Department of Clinical Physiology, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland [18]Program inGenetics and Genome Biology, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada [19]Beijing Institute of Ophthalmology, Beijing TongrenHospital, Capital Medical University, Beijing, China [20]Department of Ophthalmology, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim,Germany [21]Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland [22]Gerontology Research Center, University of Jyväskylä, Jyväskylä, Finland [23]Department of Ophthalmology, Central Hospital of Central Finland, Jyväskylä, Finland [24]Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki,Finland [25]Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong [26]Department of Ophthalmology and Visual Sciences,The Chinese University of Hong Kong, Hong Kong Eye Hospital, Kowloon, Hong Kong [27]Department of Ophthalmology and Visual Sciences, The Chinese University ofHong Kong, Prince of Wales Hospital, Shatin, Hong Kong [28]Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia [29]Department ofOphthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA [30]Estonian Genome Center, University ofTartu, Tartu, Estonia [31]Department of Pediatrics, National University of Singapore, Singapore [32]Division of Human Genetics, Genome Institute of Singapore, Singapore [33]Department of Medicine, National University of Singapore, Singapore [34]Duke–National University of Singapore Graduate Medical School, Singapore [35]A full list ofmembers appears in the Supplementary Note [36]Institute of Epidemiology I, Helmholtz Zentrum München–German Research Center for Environmental Health,Neuherberg, Germany [37]Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany [38]Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands [39]Institute of Human Genetics, Technical University Munich, Munich,Germany [40]Research Centre of Applied and Preventive Medicine, University of Turku, Turku, Finland [41]Department of Clinical Physiology and Nuclear Medicine, TurkuUniversity Hospital, Turku, Finland [42]Department of Pediatric Ophthalmology, Duke Eye Center For Human Genetics, Durham, North Carolina, USA [43]Institute ofPopulation Genetics, National Research Council, Sassari, Italy [44]School of Women’s and Infants’ Health, University of Western Australia, Perth, Western Australia,Australia [45]Department of Molecular Epidemiology, Queensland Institute of Medical Research, Herston, Brisbane, Queensland, Australia [46]Medical Research CouncilCentre of Epidemiology for Child Health, Institute of Child Health, University College London, London, UK [47]Ulverscroft Vision Research Group, University CollegeLondon, London, UK [48]Imperial College Cerebrovascular Research Unit (ICCRU), Division of Brain Sciences, Department of Medicine, Imperial College London,London, UK [49]Department of Ophthalmology, Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia [50]Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA [51]Department of Ophthalmology and Visual Sciences, CaseWestern Reserve University and University Hospitals Eye Institute, Cleveland, Ohio, USA [52]National Eye Institute, US National Institutes of Health, Bethesda, Maryland,USA [53]Department of Genetics, Case Western Reserve University, Cleveland, Ohio, USA [54]Department of Clinical and Molecular Ophthalmogenetics, NetherlandsInstitute of Neurosciences (NIN [55] an Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands [55]Centre for PopulationHealth Sciences, University of Edinburgh, Edinburgh, UK [56]Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Universityof Edinburgh, Edinburgh, UK [57]Faculty of Medicine, University of Split, Split, Croatia [58]Department of Ophthalmology, Sisters of Mercy University Hospital, Zagreb,Croatia [59]Princess Alexandra Eye Pavilion, Edinburgh, UK [60]Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany [61]Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, The Netherlands [62]Department of Clinical Genetics, Erasmus MedicalCenter, Rotterdam, The Netherlands [63]Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands [64]Department of Ophthalmology,Academic Medical Center, Amsterdam, The Netherlands [65]Department of Statistics and Applied Probability, National University of Singapore, Singapore [66]Institute ofOphthalmology, Moorfields Eye Hospital, London, UK [67]Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

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出版当年[2012]版:
大类 | 1 区 生物
小类 | 1 区 遗传学
最新[2025]版:
大类 | 1 区 生物学
小类 | 1 区 遗传学
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出版当年[2011]版:
Q1 GENETICS & HEREDITY
最新[2023]版:
Q1 GENETICS & HEREDITY

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第一作者机构: [1]Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands [2]Department of Epidemiology, Erasmus Medical Center, Rotterdam,The Netherlands
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通讯作者:
通讯机构: [1]Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands [2]Department of Epidemiology, Erasmus Medical Center, Rotterdam,The Netherlands
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