机构:[1]Genome Institute of Singapore, A-STAR, Singapore[2]Singapore Eye Research Institute, Singapore National Eye Centre and Eye ACP, Duke–National University ofSingapore, Singapore[3]Department of Biochemistry, National University of Singapore, Singapore[4]Vietnam National Institute of Ophthalmology, Hanoi, Vietnam[5]Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China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[6]Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan[7]Jadhavbhai Nathamal Singhvi Department of Glaucoma,Medical Research Foundation, Sankara Nethralaya, Chennai, India[8]Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia[9]Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, Florida, USA[10]Department of Genetics, Aravind Medical ResearchFoundation, Madurai, India[11]Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China[12]Department of Ophthalmology,Tan Tock Seng Hospital, NHG Eye Institute, Singapore[13]Department of Ophthalmology, University of the Ryukyus, Okinawa, Nishihara, Japan[14]Center of MolecularBiology and Genetic Engineering, University of Campinas, Campinas, Brazil[15]Department of Ophthalmology, School of Medical Sciences, Health Campus, UniversitiSains Malaysia and Hospital Universiti Sains Malaysia, Kelantan, Malaysia[16]Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan[17]Instituto de Glaucoma y Catarata, Lima, Peru[18]Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland[19]NIHR BiomedicalResearch Centre for Ophthalmology at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, UK[20]Glaucoma Service,Moorfields Eye Hospital NHS Foundation Trust, London, UK[21]Division of Genetics, UCL Institute of Ophthalmology, London, UK[22]Department of Ophthalmology,Medical Faculty Mannheim of the Ruprecht Karls University Heidelberg, Heidelberg, Germany[23]Ho Chi Minh City Eye Hospital, Ho Chi Minh City, Vietnam[24]Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan[25]Pakistan Institute of Ophthalmology, Al-Shifa Trust Eye Hospital,Rawalpindi, Pakistan[26]Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands[27]Department of Ophthalmology, NationalUniversity Health System, Yong Loo Lin School of Medicine, National University of Singapore, Singapore[28]King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia[29]All India Institute of Medical Sciences, New Delhi, India[30]Department of Glaucoma, Da Nang Eye Hospital, Da Nang City, Vietnam[31]Department ofOphthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia[32]Department of Ophthalmology, Faculty of Medicine SirirajHospital, Mahidol University, Bangkok, Thailand[33]Glaucoma Services, Department of Ophthalmology, Rajavithi Hospital, Bangkok, Thailand[34]College of Medicine,Rangsit University, Bangkok, Thailand[35]Mandalay Eye Department, Mandalay Eye ENT Hospital, University of Medicine Mandalay, Mandalay, Myanmar[36]Department of Ophthalmology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia[37]Vision Research Foundation, Sankara Nethralaya, Chennai, India[38]Division of Ophthalmology, Changi General Hospital, Singapore[39]Department of Ophthalmology, Thammasat University Faculty of Medicine, Rangsit, Thailand[40]Eye Department, Viet Tiep General Hospital, Hai Phong, Vietnam[41]Asian Eye Institute, Manila, Philippines[42]Division of Ophthalmology, University of the East,Manila, Philippines[43]Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea[44]Glaucoma Service Jakarta EyeCenter, Jakarta, Indonesia[45]Faculty of Medicine, University of Indonesia, Jakarta, Indonesia[46]Narayana Nethralaya Eye Hospital, Bangalore, India[47]EinhornClinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA[48]Department of Ophthalmology, Kobe City Medical CenterGeneral Hospital, Kobe, Japan[49]Nepal Glaucoma Eye Clinic, Tilganga Institute of Ophthalmology, Kathmandu, Nepal[50]Department of Ophthalmology, Faculty ofMedicine, Chiang Mai University, Chiang Mai, Thailand[51]Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK[52]Department of Ophthalmology, Konyang University, Kim’s Eye Hospital, Myung-Gok Eye Research Institute, Seoul, Republic of Korea[53]Dipartimento di Scienze Chirurgiche, Università di Torino, Turin, Italy[54]Ozaki Eye Hospital, Hyuga, Japan[55]Department of Ophthalmology, Faculty of Medicine, University of Miyazaki,Miyazaki, Japan[56]Department of Ophthalmology, University of Hong Kong, Hong Kong, China[57]Department of Ophthalmology, Faculty of Medicine, ChulalongkornUniversity, Bangkok, Thailand[58]Department of Ophthalmology, No.1 Defence Services General Hospital, Yangon, Myanmar[59]Mizoguchi Eye Hospital, Sasebo,Japan[60]Department of Ophthalmology, Oita University Faculty of Medicine, Oita, Japan[61]Department of Ophthalmology, Yonsei University College of Medicine,Seoul, Republic of Korea[62]Shijiazhuang First Eye Hospital, Shijiazhuang, China[63]Handan Eye Hospital, Handan, China[64]Eye Institute and Affiliated Xiamen EyeCenter, Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China[65]Anyang Eye Hospital, Anyang, China[66]Departmentof Ophthalmology, Pasig City General Hospital, Pasig City, Philippines[67]University of Malaya, Eye Research Centre, Kuala Lumpur, Malaysia[68]Department ofOphthalmology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia[69]Myanmar Eye Centre, Pun Hlaing Silom Hospital, Yangon, Myanmar[70]MyanmarEye Centre, Shwe La Min Hospital, Yangon, Myanmar[71]Department of Ophthalmology/Glaucoma Section, Asian Hospital and Medical Center, Muntinlupa City,Philippines[72]Binan Doctors Eye Center, Binan Doctors Hospital, Laguna, Philippines[73]Department of Ophthalmology, University Hospital Nottingham, University ofNottingham, Nottingham, UK[74]BMI Park Hospital Nottingham, Nottingham, UK[75]International Specialist Eye Centre, Kuala Lumpur, Malaysia[76]Glaucoma Clinic,Aravind Eye Hospital, Pondicherry, India[77]Glaucoma Clinic, Aravind Eye Hospital, Madurai, India[78]Department of Ophthalmology, Faculty of Medical Sciences,University of Campinas, Campinas, Brazil[79]Instituto de Ciencias Médicas, Lima, Peru[80]Hospital Nacional Arzobispo Loayza, Lima, Peru[81]Centro de Genética yBiología Molecular, Universidad de San Martín de Porres, Lima, Peru[82]Wilmer Eye Institute, Johns Hopkins Hospital School of Medicine, Baltimore, Maryland, USA[83]Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands[84]Menzies Institute for Medical Research, University of Tasmania,Hobart, Tasmania, Australia[85]Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia[86]Department of Ophthalmology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand中山大学附属第二医院[87]Department of Ophthalmology, Queen Mary Hospital, Hong Kong, China[88]Department of Ophthalmology, North Okkalarpa General Hospital, Yangon, Myanmar[89]Institute for Human Genetics, University of California, San Francisco, SanFrancisco, California, USA[90]Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam[91]Peter Doherty Institute for Infection and Immunity, University ofMelbourne, Melbourne, Victoria, Australia[92]Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam[93]Sun Yat-Sen University Cancer Center, State Key Laboratoryof Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China[94]Department of Experimental Research, Sun Yat-sen UniversityCancer Center, Guangzhou, China[95]Peking Union Medical College, Beijing, China[96]Oxford University Clinical Research Unit–Nepal, Patan Academy of HealthSciences, Patan Hospital, Patan, Nepal[97]Institute of Human Genetics, Friedrich Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany[98]Departmentof Ophthalmology, Monfalcone Hospital, Gorizia, Italy[99]Department of Surgery, Section of Ophthalmology, University of Siena, Siena, Italy[100]Centre for VisionResearch, Department of Ophthalmology, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia[101]Department ofOphthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA[102]Wynn Institute for Vision Research, University of Iowa,Iowa City, Iowa, USA[103]Department of Ophthalmology, Duke University Eye Center, Durham, North Carolina, USA[104]Department of Medicine, Duke UniversityMedical Center, Durham, North Carolina, USA[105]Division of Medical Oncology, National Cancer Centre, Singapore[106]Department of Economics, National Universityof Singapore, Singapore[107]Department of Psychology, National University of Singapore, Singapore[108]Institut Pasteur, Functional Genetics of Infectious DiseasesUnit, Department of Genomes and Genetics, Paris, France[109]Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, Paris, France[110]Department of Ophthalmology, Seoul National University Bundang Hospital, Gyeonggi, Republic of Korea[111]Department of Ophthalmology, Seoul MetropolitanGovernment Seoul National University Boramae Medical Center, Seoul, Republic of Korea[112]Department of Medical Microbiology and Virology, University MedicalCenter Utrecht, Utrecht, the Netherlands[113]GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India[114]Department of Biochemistry,Al-Nafees Medical College and Hospital, Isra University, Islamabad, Pakistan[115]Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital MedicalUniversity, 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[116]Saw Swee Hock School of Public Health, National University of Singapore, Singapore[117]Life Sciences Institute, National University ofSingapore, Singapore[118]National University of Singapore Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore[119]Department of Statistics and Applied Probability, National University of Singapore, Singapore[120]Department of Medicine, Yong Loo Lin School of Medicine,National University of Singapore, Singapore[121]Department of Glaucoma, Institute of Ophthalmology ‘Conde de Valenciana’, Mexico City, Mexico[122]Department ofGenetics, Institute of Ophthalmology ‘Conde de Valenciana’, Mexico City, Mexico[123]Department of Biochemistry, Faculty of Medicine, Universidad NacionalAutónoma de México, Mexico City, Mexico
Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 x 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 x 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 x 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 x 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 x 10(-12)). We also confirmed significant association at three previously described loci (P < 5 x 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18)(1), providing new insights into the biology of PACG.
基金:
Singapore Ministry of Health's National Medical Research Council under its Translational and Clinical Research (TCR) Flagship Programme Grant Stratified Medicine for Primary Angle Closure GlaucomaMinistry of Health-SingaporeNational Medical Research Council, Singapore [NMRC/TCR/008-SERI/2013]; Singapore Translational Research (STaR) Investigator Award Singapore Angle Closure Glaucoma Program Characterization, Prevention, and Management [NMRC/STAR/0023/2014]; Biomedical Research CouncilAgency for Science Technology & Research (ASTAR); Agency for Science, Technology and Research (A-STAR), SingaporeAgency for Science Technology & Research (ASTAR); Universiti Sains MalaysiaUniversiti Sains Malaysia [RUI 1001/PPSP/812101, RUI 1001/PPSP/812152]; Program of Beijing Scholars; Leading Talents-High-Level Talents of the Health System of Beijing [2009-1-05]; National Major Scientific and Technological Special Project for 'Significant New Drugs Development' [2011ZX09302-007-05]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81570837]; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MR/K006584/1] Funding Source: researchfish; National Institute for Health ResearchNational Institute for Health Research (NIHR) [CL-2013-18-012] Funding Source: researchfish
第一作者机构:[1]Genome Institute of Singapore, A-STAR, Singapore[3]Department of Biochemistry, National University of Singapore, Singapore
共同第一作者:
通讯作者:
通讯机构:[1]Genome Institute of Singapore, A-STAR, Singapore[2]Singapore Eye Research Institute, Singapore National Eye Centre and Eye ACP, Duke–National University ofSingapore, Singapore[3]Department of Biochemistry, National University of Singapore, Singapore[5]Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China[27]Department of Ophthalmology, NationalUniversity Health System, Yong Loo Lin School of Medicine, National University of Singapore, Singapore[115]Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital MedicalUniversity, Beijing, China
推荐引用方式(GB/T 7714):
Chiea Chuen Khor–,Tan Do,Hongyan Jia,et al.Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma[J].NATURE GENETICS.2016,48(5):556-+.doi:10.1038/ng.3540.
APA:
Chiea Chuen Khor–,Tan Do,Hongyan Jia,Masakazu Nakano,Ronnie George...&Tin Aung.(2016).Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma.NATURE GENETICS,48,(5)
MLA:
Chiea Chuen Khor–,et al."Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma".NATURE GENETICS 48..5(2016):556-+