Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium
机构:[1]Centre for Quantitative Medicine, Duke-NUS Medial School, Singapore[2]Department of Statistical Science, Schoolof Mathematics & Computational Science, Sun Yat-Sen University, Guangzhou, China[3]State Key Laboratoryof Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China[4]Department ofEpidemiology, Erasmus Medical Center, Rotterdam, The Netherlands[5]Department of Ophthalmology, ErasmusMedical Center, Rotterdam, The Netherlands[6]Department of Ophthalmology, King’s College London, St Thomas’Hospital campus, London, UK[7]Department of Twin Research and Genetic Epidemiology, King’s College LondonSchool of Medicine, London, UK[8]Centre for Ophthalmology and Visual Science, Lions Eye Institute, Universityof Western Australia, Perth, Australia[9]Genetics and Genome Biology Program, Hospital for Sick Children andUniversity of Toronto, Toronto, Ontario, Canada[10]MRC Integrative Epidemiology Unit (IEU) at the University ofBristol, Bristol, UK[11]School of Social and Community Medicine, University of Bristol, Bristol, UK[12]Max PlanckInstitute for Psycholinguistics, Wundtlaan 1, 6525 XD Nijmegen, The Netherlands[13]University of QueenslandDiamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia[14]MRC Social, Genetic andDevelopmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London,London, UK[15]Beijing Institute of Ophthalmology, 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]Beijing Ophthalmology and Visual Science Key Lab, Beijing, China首都医科大学附属同仁医院[17]Department of Ophthalmology, MedicalFaculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany[18]Centre for Eye Research Australia(CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia[19]Centre forVision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney,Sydney, Australia[20]Department of Ophthalmology, National University Health Systems, National University ofSingapore, Singapore[21]Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore[22]Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore[23]SawSwee Hock School of Public Health, National University Health Systems, National University of Singapore, Singapore,Singapore[24]Computational and Statistical Genomics Branch, National Human Genome Research Institute, NationalInstitutes of Health, Baltimore, MD, USA[25]Department of Epidemiology, Johns Hopkins Bloomberg School ofPublic Health, Baltimore, Maryland, USA[26]Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore,MD[27]Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA[28]Duke-NationalUniversity of Singapore Graduate Medical School, Singapore, Singapore[29]Department of Health Sciences andGerontology Research Center, University of Jyväskylä, Jyväskylä, Finland[30]Department of Ophthalmology,Central Hospital of Central Finland, Jyväskylä, Finland[31]Institute of Human Genetics, Technical University Munich,Munich, Germany[32]Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany[33]School ofOptometry & Vision Sciences, Cardiff University, Cardiff, UK
Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).
基金:
Wellcome TrustWellcome TrustEuropean Commission [102215/2/13/2]; UK Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MC_UU_12013/3, MC_UU_12013/4, G0901245, G0500079]; Hong Kong Polytechnic UniversityHong Kong Polytechnic University [Z0GM]; Australian National Health and Medical Research Council (NHMRC)National Health and Medical Research Council of Australia; NHMRC Medical Genomics GrantNational Health and Medical Research Council of Australia; National Institutes of Health (NIH)/National Eye Institute (NEI)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Eye Institute (NEI) [RO1EY018246]; Clifford Craig Medical Research Trust; Ophthalmic Research Institute of Australia (ORIA); American Health Assistance Foundation (AHAF); Peggy and Leslie Cranbourne Foundation; Foundation for Children; NHMRCNational Health and Medical Research Council of Australia [350415]; Center for Inherited Diseases Research (CIDR); National Science FoundationNational Science Foundation (NSF) [81125007]; Fundamental Research Funds for the State Key Laboratory, NSFC [11401600]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [15lgpy07]; SYSU-CMU Shunde International Joint Research Institute; 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)National Health and Medical Research Council of Australia [1021105]; LEI; Australian Foundation for the Prevention of Blindness; Singapore BioMedical Research Council (BMRC)Agency for Science Technology & Research (ASTAR); Singapore Tissue Network; NMRCNational Medical Research Council, Singapore [1176/2008]; US National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [HD044454, HD059215]; Medical Research Council Research Professorship awardUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [G19/2]; European Research Council Advanced Investigator awardEuropean Research Council (ERC) [295366]; Medical Research Council Clinical Research Training FellowshipUK Research & Innovation (UKRI)Medical Research Council UK (MRC); Institute of Psychiatry, Psychology and Neuroscience Excellence Studentship; National Eye Institute, National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Eye Institute (NEI) [R01-EY016379]; Research to Prevent Blindness, New York, NYResearch to Prevent Blindness (RPB); Intramural Research Program of the National Human Genome Research Institute, NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI); Research to Prevent Blindness, Inc.Research to Prevent Blindness (RPB); NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NEI R01EY014685]; Jack Brockhoff Foundation; Pfizer Australia Senior Research FellowshipPfizerPfizer Australia; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_PC_13048, MC_UU_12013/3, MR/K023721/1, G1000143, G0500079, G0901245, MC_UU_12015/1, MC_UU_12013/5, MC_UU_12013/4, MR/N003284/1, G19/2, MC_U106179471, MC_PC_15018, G0401527] Funding Source: researchfish; National Institute for Health ResearchNational Institute for Health Research (NIHR) [SRF-2015-08-005, NF-SI-0512-10114, SRF/01/010] Funding Source: researchfish; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [G0901245, MC_UU_12015/1, MR/N003284/1, MC_UU_12013/4, MC_UU_12013/3, G0500079, MR/K023721/1, G19/2, MC_UU_12013/5] Funding Source: UKRI; EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENTUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [R01HD059215, R01HD044454] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Eye Institute (NEI) [R01EY014685, K08EY022943, R01EY023196, R01EY018246, P30EY001583, R01EY016379, R01EY024233] Funding Source: NIH RePORTER; 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
第一作者机构:[1]Centre for Quantitative Medicine, Duke-NUS Medial School, Singapore
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推荐引用方式(GB/T 7714):
Qiao Fan,XiaoboGuo,J.Willem L.Tideman,et al.Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium[J].SCIENTIFIC REPORTS.2016,6:doi:10.1038/srep25853.
APA:
Qiao Fan,XiaoboGuo,J.Willem L.Tideman,Katie M.Williams,SeyhanYazar...&JeremyA.Guggenheim.(2016).Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium.SCIENTIFIC REPORTS,6,
MLA:
Qiao Fan,et al."Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium".SCIENTIFIC REPORTS 6.(2016)