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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genome-wide analysis of multiethnic cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma</title><author><name sortKey="Hysi, Pirro G" sort="Hysi, Pirro G" uniqKey="Hysi P" first="Pirro G" last="Hysi">Pirro G. Hysi</name><affiliation><nlm:aff id="A1">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Cheng, Ching Yu" sort="Cheng, Ching Yu" uniqKey="Cheng C" first="Ching-Yu" last="Cheng">Ching-Yu Cheng</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Duke-National University of Singapore, Graduate Medical School, Singapore</nlm:aff></affiliation></author><author><name sortKey="Springelkamp, Henriet" sort="Springelkamp, Henriet" uniqKey="Springelkamp H" first="Henriët" last="Springelkamp">Henriët Springelkamp</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Macgregor, Stuart" sort="Macgregor, Stuart" uniqKey="Macgregor S" first="Stuart" last="Macgregor">Stuart Macgregor</name><affiliation><nlm:aff id="A8">Statistical Genetics, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Australia 4029</nlm:aff></affiliation></author><author><name sortKey="Bailey, Jessica N Cooke" sort="Bailey, Jessica N Cooke" uniqKey="Bailey J" first="Jessica N Cooke" last="Bailey">Jessica N Cooke Bailey</name><affiliation><nlm:aff id="A9">Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Wojciechowski, Robert" sort="Wojciechowski, Robert" uniqKey="Wojciechowski R" first="Robert" last="Wojciechowski">Robert Wojciechowski</name><affiliation><nlm:aff id="A10">Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health and, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A11">National Human Genome Research Institute, National Institutes of Health, Baltimore, MD 21224, USA</nlm:aff></affiliation></author><author><name sortKey="Vitart, Veronique" sort="Vitart, Veronique" uniqKey="Vitart V" first="Veronique" last="Vitart">Veronique Vitart</name><affiliation><nlm:aff id="A12">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh</nlm:aff></affiliation></author><author><name sortKey="Nag, Abhishek" sort="Nag, Abhishek" uniqKey="Nag A" first="Abhishek" last="Nag">Abhishek Nag</name><affiliation><nlm:aff id="A1">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Hewitt, Alex W" sort="Hewitt, Alex W" uniqKey="Hewitt A" first="Alex W" last="Hewitt">Alex W. Hewitt</name><affiliation><nlm:aff id="A13">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia</nlm:aff></affiliation></author><author><name sortKey="Hohn, Rene" sort="Hohn, Rene" uniqKey="Hohn R" first="René" last="Höhn">René Höhn</name><affiliation><nlm:aff id="A14">Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="Venturini, Cristina" sort="Venturini, Cristina" uniqKey="Venturini C" first="Cristina" last="Venturini">Cristina Venturini</name><affiliation><nlm:aff id="A1">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A15">Institute of Ophthalmology, University College London, UK</nlm:aff></affiliation></author><author><name sortKey="Mirshahi, Alireza" sort="Mirshahi, Alireza" uniqKey="Mirshahi A" first="Alireza" last="Mirshahi">Alireza Mirshahi</name><affiliation><nlm:aff id="A14">Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="Ramdas, Wishal D" sort="Ramdas, Wishal D" uniqKey="Ramdas W" first="Wishal D." last="Ramdas">Wishal D. Ramdas</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Thorleifsson, Gudmar" sort="Thorleifsson, Gudmar" uniqKey="Thorleifsson G" first="Gudmar" last="Thorleifsson">Gudmar Thorleifsson</name><affiliation><nlm:aff id="A16">deCODE/Amgen, 101 Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Vithana, Eranga" sort="Vithana, Eranga" uniqKey="Vithana E" first="Eranga" last="Vithana">Eranga Vithana</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Duke-National University of Singapore, Graduate Medical School, Singapore</nlm:aff></affiliation></author><author><name sortKey="Khor, Chiea Chuen" sort="Khor, Chiea Chuen" uniqKey="Khor C" first="Chiea-Chuen" last="Khor">Chiea-Chuen Khor</name><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Division of Human Genetics, Genome Institute of Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Arni B" sort="Stefansson, Arni B" uniqKey="Stefansson A" first="Arni B" last="Stefansson">Arni B. Stefansson</name><affiliation><nlm:aff id="A18">Eye Clinic, 105 Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Liao, Jiemin" sort="Liao, Jiemin" uniqKey="Liao J" first="Jiemin" last="Liao">Jiemin Liao</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation></author><author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan L" last="Haines">Jonathan L. Haines</name><affiliation><nlm:aff id="A9">Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Amin, Najaf" sort="Amin, Najaf" uniqKey="Amin N" first="Najaf" last="Amin">Najaf Amin</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wang, Ya Xing" sort="Wang, Ya Xing" uniqKey="Wang Y" first="Ya Xing" last="Wang">Ya Xing Wang</name><affiliation><nlm:aff id="A19">Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China 100730</nlm:aff></affiliation></author><author><name sortKey="Wild, Philipp S" sort="Wild, Philipp S" uniqKey="Wild P" first="Philipp S" last="Wild">Philipp S. Wild</name><affiliation><nlm:aff id="A20">Department of Internal Medicine II, University Medical Center Mainz, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="Ozel, Ayse B" sort="Ozel, Ayse B" uniqKey="Ozel A" first="Ayse B" last="Ozel">Ayse B. Ozel</name><affiliation><nlm:aff id="A21">Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Li, Jun Z" sort="Li, Jun Z" uniqKey="Li J" first="Jun Z" last="Li">Jun Z. Li</name><affiliation><nlm:aff id="A21">Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Fleck, Brian W" sort="Fleck, Brian W" uniqKey="Fleck B" first="Brian W" last="Fleck">Brian W. Fleck</name><affiliation><nlm:aff id="A22">NHS Princess Alexandra Eye Pavilion, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Zeller, Tanja" sort="Zeller, Tanja" uniqKey="Zeller T" first="Tanja" last="Zeller">Tanja Zeller</name><affiliation><nlm:aff id="A23">Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Staffieri, Sandra E" sort="Staffieri, Sandra E" uniqKey="Staffieri S" first="Sandra E" last="Staffieri">Sandra E. Staffieri</name><affiliation><nlm:aff id="A13">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia</nlm:aff></affiliation></author><author><name sortKey="Teo, Yik Ying" sort="Teo, Yik Ying" uniqKey="Teo Y" first="Yik-Ying" last="Teo">Yik-Ying Teo</name><affiliation><nlm:aff id="A4">Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A24">Department of Statistics and Applied Probability, National University of Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Cuellar Partida, Gabriel" sort="Cuellar Partida, Gabriel" uniqKey="Cuellar Partida G" first="Gabriel" last="Cuellar-Partida">Gabriel Cuellar-Partida</name><affiliation><nlm:aff id="A8">Statistical Genetics, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Australia 4029</nlm:aff></affiliation></author><author><name sortKey="Luo, Xiaoyan" sort="Luo, Xiaoyan" uniqKey="Luo X" first="Xiaoyan" last="Luo">Xiaoyan Luo</name><affiliation><nlm:aff id="A25">Duke University, Duke Eye Center, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Allingham, R Rand" sort="Allingham, R Rand" uniqKey="Allingham R" first="R Rand" last="Allingham">R Rand Allingham</name><affiliation><nlm:aff id="A26">Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Richards, Julia E" sort="Richards, Julia E" uniqKey="Richards J" first="Julia E" last="Richards">Julia E. Richards</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Senft, Andrea" sort="Senft, Andrea" uniqKey="Senft A" first="Andrea" last="Senft">Andrea Senft</name><affiliation><nlm:aff id="A27">Institute of Medical Biometry and Statistics, University Hospital Schleswig-Holstein, Lübeck, Germany</nlm:aff></affiliation></author><author><name sortKey="Karssen, Lennart C" sort="Karssen, Lennart C" uniqKey="Karssen L" first="Lennart C" last="Karssen">Lennart C. Karssen</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zheng, Yingfeng" sort="Zheng, Yingfeng" uniqKey="Zheng Y" first="Yingfeng" last="Zheng">Yingfeng Zheng</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation></author><author><name sortKey="Bellenguez, Celine" sort="Bellenguez, Celine" uniqKey="Bellenguez C" first="Céline" last="Bellenguez">Céline Bellenguez</name><affiliation><nlm:aff id="A28">Inserm, UMR774, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Université Lille 2, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Institut Pasteur de Lille, France</nlm:aff></affiliation></author><author><name sortKey="Xu, Liang" sort="Xu, Liang" uniqKey="Xu L" first="Liang" last="Xu">Liang Xu</name><affiliation><nlm:aff id="A19">Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China 100730</nlm:aff></affiliation></author><author><name sortKey="Iglesias, Adriana I" sort="Iglesias, Adriana I" uniqKey="Iglesias A" first="Adriana I" last="Iglesias">Adriana I. Iglesias</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wilson, James F" sort="Wilson, James F" uniqKey="Wilson J" first="James F" last="Wilson">James F. Wilson</name><affiliation><nlm:aff id="A31">Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Kang, Jae H" sort="Kang, Jae H" uniqKey="Kang J" first="Jae H" last="Kang">Jae H. Kang</name><affiliation><nlm:aff id="A32">Channing Division of Network Medicine, Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Van Leeuwen, Elisabeth M" sort="Van Leeuwen, Elisabeth M" uniqKey="Van Leeuwen E" first="Elisabeth M" last="Van Leeuwen">Elisabeth M. Van Leeuwen</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Jonsson, Vesteinn" sort="Jonsson, Vesteinn" uniqKey="Jonsson V" first="Vesteinn" last="Jonsson">Vesteinn Jonsson</name><affiliation><nlm:aff id="A33">Department of Ophthalmology, Landspitali National University Hospital, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Thorsteinsdottir, Unnur" sort="Thorsteinsdottir, Unnur" uniqKey="Thorsteinsdottir U" first="Unnur" last="Thorsteinsdottir">Unnur Thorsteinsdottir</name><affiliation><nlm:aff id="A16">deCODE/Amgen, 101 Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Despriet, Dominiek D G" sort="Despriet, Dominiek D G" uniqKey="Despriet D" first="Dominiek D. G." last="Despriet">Dominiek D. G. Despriet</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ennis, Sarah" sort="Ennis, Sarah" uniqKey="Ennis S" first="Sarah" last="Ennis">Sarah Ennis</name><affiliation><nlm:aff id="A34">Human Genetics & Genomic Medicine, Faulty of Medicine, University of Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Moroi, Sayoko E" sort="Moroi, Sayoko E" uniqKey="Moroi S" first="Sayoko E" last="Moroi">Sayoko E. Moroi</name><affiliation><nlm:aff id="A35">Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G" last="Martin">Nicholas G. Martin</name><affiliation><nlm:aff id="A36">Genetic Epidemiology, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Jansonius, Nomdo M" sort="Jansonius, Nomdo M" uniqKey="Jansonius N" first="Nomdo M" last="Jansonius">Nomdo M. Jansonius</name><affiliation><nlm:aff id="A37">Department of Ophthalmology, University Medical Center Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Yazar, Seyhan" sort="Yazar, Seyhan" uniqKey="Yazar S" first="Seyhan" last="Yazar">Seyhan Yazar</name><affiliation><nlm:aff id="A38">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.</nlm:aff></affiliation></author><author><name sortKey="Tai, E Shyong" sort="Tai, E Shyong" uniqKey="Tai E" first="E-Shyong" last="Tai">E-Shyong Tai</name><affiliation><nlm:aff id="A4">Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Duke-National University of Singapore, Graduate Medical School, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Medicine, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation></author><author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name><affiliation><nlm:aff id="A27">Institute of Medical Biometry and Statistics, University Hospital Schleswig-Holstein, Lübeck, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Inserm, UMR774, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Université Lille 2, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A40">Centre Hospitalier Régional Universitaire de Lille, France</nlm:aff></affiliation></author><author><name sortKey="Kirwan, James" sort="Kirwan, James" uniqKey="Kirwan J" first="James" last="Kirwan">James Kirwan</name><affiliation><nlm:aff id="A41">Department of Ophthalmology, Portsmouth Hospitals NHS Trust, Portsmouth, UK</nlm:aff></affiliation></author><author><name sortKey="Van Koolwijk, Leonieke M E" sort="Van Koolwijk, Leonieke M E" uniqKey="Van Koolwijk L" first="Leonieke M. E." last="Van Koolwijk">Leonieke M. E. Van Koolwijk</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael A" last="Hauser">Michael A. Hauser</name><affiliation><nlm:aff id="A26">Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A42">Department of Medicine, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Jonasson, Fridbert" sort="Jonasson, Fridbert" uniqKey="Jonasson F" first="Fridbert" last="Jonasson">Fridbert Jonasson</name><affiliation><nlm:aff id="A43">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Leo, Paul" sort="Leo, Paul" uniqKey="Leo P" first="Paul" last="Leo">Paul Leo</name><affiliation><nlm:aff id="A44">The University of Queensland, Diamantina Institute, Woollongabba, Australia</nlm:aff></affiliation></author><author><name sortKey="Loomis, Stephanie J" sort="Loomis, Stephanie J" uniqKey="Loomis S" first="Stephanie J" last="Loomis">Stephanie J. Loomis</name><affiliation><nlm:aff id="A45">Dept. Ophthalmology Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Fogarty, Rhys" sort="Fogarty, Rhys" uniqKey="Fogarty R" first="Rhys" last="Fogarty">Rhys Fogarty</name><affiliation><nlm:aff id="A46">Department of Ophthalmology, Flinders University, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Kearns, Lisa" sort="Kearns, Lisa" uniqKey="Kearns L" first="Lisa" last="Kearns">Lisa Kearns</name><affiliation><nlm:aff id="A13">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia</nlm:aff></affiliation></author><author><name sortKey="Lackner, Karl J" sort="Lackner, Karl J" uniqKey="Lackner K" first="Karl J" last="Lackner">Karl J. Lackner</name><affiliation><nlm:aff id="A49">Institute of Clinical Chemistry and Laboratory Medicine, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="De Jong, Paulus T V M" sort="De Jong, Paulus T V M" uniqKey="De Jong P" first="Paulus T. V. M." last="De Jong">Paulus T. V. M. De Jong</name><affiliation><nlm:aff id="A50">Netherlands Institute for Neuroscience, Amsterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A51">Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A52">Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Simpson, Claire L" sort="Simpson, Claire L" uniqKey="Simpson C" first="Claire L" last="Simpson">Claire L. Simpson</name><affiliation><nlm:aff id="A11">National Human Genome Research Institute, National Institutes of Health, Baltimore, MD 21224, USA</nlm:aff></affiliation></author><author><name sortKey="Pennell, Craig E" sort="Pennell, Craig E" uniqKey="Pennell C" first="Craig E" last="Pennell">Craig E. Pennell</name><affiliation><nlm:aff id="A53">School of Women’s and Infants’ Health, The University of Western Australia, Perth, Australia</nlm:aff></affiliation></author><author><name sortKey="Oostra, Ben A" sort="Oostra, Ben A" uniqKey="Oostra B" first="Ben A" last="Oostra">Ben A. Oostra</name><affiliation><nlm:aff id="A54">Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G" last="Uitterlinden">André G. Uitterlinden</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Saw, Seang Mei" sort="Saw, Seang Mei" uniqKey="Saw S" first="Seang-Mei" last="Saw">Seang-Mei Saw</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Duke-National University of Singapore, Graduate Medical School, Singapore</nlm:aff></affiliation></author><author><name sortKey="Lotery, Andrew J" sort="Lotery, Andrew J" uniqKey="Lotery A" first="Andrew J" last="Lotery">Andrew J. Lotery</name><affiliation><nlm:aff id="A55">Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Bailey Wilson, Joan E" sort="Bailey Wilson, Joan E" uniqKey="Bailey Wilson J" first="Joan E" last="Bailey-Wilson">Joan E. Bailey-Wilson</name><affiliation><nlm:aff id="A11">National Human Genome Research Institute, National Institutes of Health, Baltimore, MD 21224, USA</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vingerling, Johannes R" sort="Vingerling, Johannes R" uniqKey="Vingerling J" first="Johannes R" last="Vingerling">Johannes R. Vingerling</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Maubaret, Cecilia" sort="Maubaret, Cecilia" uniqKey="Maubaret C" first="Cécilia" last="Maubaret">Cécilia Maubaret</name><affiliation><nlm:aff id="A56">Univ. Bordeaux, ISPED, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A57">Inserm, Centre INSERM U897-Epidemiologie-Biostatistique Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Pfeiffer, Norbert" sort="Pfeiffer, Norbert" uniqKey="Pfeiffer N" first="Norbert" last="Pfeiffer">Norbert Pfeiffer</name><affiliation><nlm:aff id="A14">Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="Wolfs, Roger C W" sort="Wolfs, Roger C W" uniqKey="Wolfs R" first="Roger C. W." last="Wolfs">Roger C. W. Wolfs</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Lemij, Hans G" sort="Lemij, Hans G" uniqKey="Lemij H" first="Hans G" last="Lemij">Hans G. Lemij</name><affiliation><nlm:aff id="A58">Glaucoma Service, the Rotterdam Eye Hospital, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Young, Terri L" sort="Young, Terri L" uniqKey="Young T" first="Terri L" last="Young">Terri L. Young</name><affiliation><nlm:aff id="A25">Duke University, Duke Eye Center, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Pasquale, Louis R" sort="Pasquale, Louis R" uniqKey="Pasquale L" first="Louis R" last="Pasquale">Louis R. Pasquale</name><affiliation><nlm:aff id="A32">Channing Division of Network Medicine, Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A45">Dept. Ophthalmology Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Delcourt, Cecile" sort="Delcourt, Cecile" uniqKey="Delcourt C" first="Cécile" last="Delcourt">Cécile Delcourt</name><affiliation><nlm:aff id="A56">Univ. Bordeaux, ISPED, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A57">Inserm, Centre INSERM U897-Epidemiologie-Biostatistique Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Spector, Timothy D" sort="Spector, Timothy D" uniqKey="Spector T" first="Timothy D" last="Spector">Timothy D. Spector</name><affiliation><nlm:aff id="A1">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Klaver, Caroline C W" sort="Klaver, Caroline C W" uniqKey="Klaver C" first="Caroline C. W." last="Klaver">Caroline C. W. Klaver</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Small, Kerrin S" sort="Small, Kerrin S" uniqKey="Small K" first="Kerrin S" last="Small">Kerrin S. Small</name><affiliation><nlm:aff id="A1">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Burdon, Kathryn P" sort="Burdon, Kathryn P" uniqKey="Burdon K" first="Kathryn P" last="Burdon">Kathryn P. Burdon</name><affiliation><nlm:aff id="A46">Department of Ophthalmology, Flinders University, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation><nlm:aff id="A16">deCODE/Amgen, 101 Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Wong, Tien Yin" sort="Wong, Tien Yin" uniqKey="Wong T" first="Tien-Yin" last="Wong">Tien-Yin Wong</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation></author><author><name sortKey="Viswanathan, Ananth" sort="Viswanathan, Ananth" uniqKey="Viswanathan A" first="Ananth" last="Viswanathan">Ananth Viswanathan</name><affiliation><nlm:aff id="A60">NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Mackey, David A" sort="Mackey, David A" uniqKey="Mackey D" first="David A" last="Mackey">David A. Mackey</name><affiliation><nlm:aff id="A13">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A38">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.</nlm:aff></affiliation></author><author><name sortKey="Craig, Jamie E" sort="Craig, Jamie E" uniqKey="Craig J" first="Jamie E" last="Craig">Jamie E. Craig</name><affiliation><nlm:aff id="A46">Department of Ophthalmology, Flinders University, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Wiggs, Janey L" sort="Wiggs, Janey L" uniqKey="Wiggs J" first="Janey L" last="Wiggs">Janey L. Wiggs</name><affiliation><nlm:aff id="A45">Dept. Ophthalmology Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M" last="Van Duijn">Cornelia M. Van Duijn</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Hammond, Christopher J" sort="Hammond, Christopher J" uniqKey="Hammond C" first="Christopher J" last="Hammond">Christopher J. Hammond</name><affiliation><nlm:aff id="A1">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Aung, Tin" sort="Aung, Tin" uniqKey="Aung T" first="Tin" last="Aung">Tin Aung</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25173106</idno><idno type="pmc">4177225</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177225</idno><idno type="RBID">PMC:4177225</idno><idno type="doi">10.1038/ng.3087</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">002E36</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E36</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-wide analysis of multiethnic cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma</title><author><name sortKey="Hysi, Pirro G" sort="Hysi, Pirro G" uniqKey="Hysi P" first="Pirro G" last="Hysi">Pirro G. Hysi</name><affiliation><nlm:aff id="A1">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Cheng, Ching Yu" sort="Cheng, Ching Yu" uniqKey="Cheng C" first="Ching-Yu" last="Cheng">Ching-Yu Cheng</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Duke-National University of Singapore, Graduate Medical School, Singapore</nlm:aff></affiliation></author><author><name sortKey="Springelkamp, Henriet" sort="Springelkamp, Henriet" uniqKey="Springelkamp H" first="Henriët" last="Springelkamp">Henriët Springelkamp</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Macgregor, Stuart" sort="Macgregor, Stuart" uniqKey="Macgregor S" first="Stuart" last="Macgregor">Stuart Macgregor</name><affiliation><nlm:aff id="A8">Statistical Genetics, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Australia 4029</nlm:aff></affiliation></author><author><name sortKey="Bailey, Jessica N Cooke" sort="Bailey, Jessica N Cooke" uniqKey="Bailey J" first="Jessica N Cooke" last="Bailey">Jessica N Cooke Bailey</name><affiliation><nlm:aff id="A9">Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Wojciechowski, Robert" sort="Wojciechowski, Robert" uniqKey="Wojciechowski R" first="Robert" last="Wojciechowski">Robert Wojciechowski</name><affiliation><nlm:aff id="A10">Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health and, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A11">National Human Genome Research Institute, National Institutes of Health, Baltimore, MD 21224, USA</nlm:aff></affiliation></author><author><name sortKey="Vitart, Veronique" sort="Vitart, Veronique" uniqKey="Vitart V" first="Veronique" last="Vitart">Veronique Vitart</name><affiliation><nlm:aff id="A12">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh</nlm:aff></affiliation></author><author><name sortKey="Nag, Abhishek" sort="Nag, Abhishek" uniqKey="Nag A" first="Abhishek" last="Nag">Abhishek Nag</name><affiliation><nlm:aff id="A1">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Hewitt, Alex W" sort="Hewitt, Alex W" uniqKey="Hewitt A" first="Alex W" last="Hewitt">Alex W. Hewitt</name><affiliation><nlm:aff id="A13">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia</nlm:aff></affiliation></author><author><name sortKey="Hohn, Rene" sort="Hohn, Rene" uniqKey="Hohn R" first="René" last="Höhn">René Höhn</name><affiliation><nlm:aff id="A14">Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="Venturini, Cristina" sort="Venturini, Cristina" uniqKey="Venturini C" first="Cristina" last="Venturini">Cristina Venturini</name><affiliation><nlm:aff id="A1">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A15">Institute of Ophthalmology, University College London, UK</nlm:aff></affiliation></author><author><name sortKey="Mirshahi, Alireza" sort="Mirshahi, Alireza" uniqKey="Mirshahi A" first="Alireza" last="Mirshahi">Alireza Mirshahi</name><affiliation><nlm:aff id="A14">Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="Ramdas, Wishal D" sort="Ramdas, Wishal D" uniqKey="Ramdas W" first="Wishal D." last="Ramdas">Wishal D. Ramdas</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Thorleifsson, Gudmar" sort="Thorleifsson, Gudmar" uniqKey="Thorleifsson G" first="Gudmar" last="Thorleifsson">Gudmar Thorleifsson</name><affiliation><nlm:aff id="A16">deCODE/Amgen, 101 Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Vithana, Eranga" sort="Vithana, Eranga" uniqKey="Vithana E" first="Eranga" last="Vithana">Eranga Vithana</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Duke-National University of Singapore, Graduate Medical School, Singapore</nlm:aff></affiliation></author><author><name sortKey="Khor, Chiea Chuen" sort="Khor, Chiea Chuen" uniqKey="Khor C" first="Chiea-Chuen" last="Khor">Chiea-Chuen Khor</name><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Division of Human Genetics, Genome Institute of Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Arni B" sort="Stefansson, Arni B" uniqKey="Stefansson A" first="Arni B" last="Stefansson">Arni B. Stefansson</name><affiliation><nlm:aff id="A18">Eye Clinic, 105 Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Liao, Jiemin" sort="Liao, Jiemin" uniqKey="Liao J" first="Jiemin" last="Liao">Jiemin Liao</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation></author><author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan L" last="Haines">Jonathan L. Haines</name><affiliation><nlm:aff id="A9">Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Amin, Najaf" sort="Amin, Najaf" uniqKey="Amin N" first="Najaf" last="Amin">Najaf Amin</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wang, Ya Xing" sort="Wang, Ya Xing" uniqKey="Wang Y" first="Ya Xing" last="Wang">Ya Xing Wang</name><affiliation><nlm:aff id="A19">Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China 100730</nlm:aff></affiliation></author><author><name sortKey="Wild, Philipp S" sort="Wild, Philipp S" uniqKey="Wild P" first="Philipp S" last="Wild">Philipp S. Wild</name><affiliation><nlm:aff id="A20">Department of Internal Medicine II, University Medical Center Mainz, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="Ozel, Ayse B" sort="Ozel, Ayse B" uniqKey="Ozel A" first="Ayse B" last="Ozel">Ayse B. Ozel</name><affiliation><nlm:aff id="A21">Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Li, Jun Z" sort="Li, Jun Z" uniqKey="Li J" first="Jun Z" last="Li">Jun Z. Li</name><affiliation><nlm:aff id="A21">Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Fleck, Brian W" sort="Fleck, Brian W" uniqKey="Fleck B" first="Brian W" last="Fleck">Brian W. Fleck</name><affiliation><nlm:aff id="A22">NHS Princess Alexandra Eye Pavilion, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Zeller, Tanja" sort="Zeller, Tanja" uniqKey="Zeller T" first="Tanja" last="Zeller">Tanja Zeller</name><affiliation><nlm:aff id="A23">Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Staffieri, Sandra E" sort="Staffieri, Sandra E" uniqKey="Staffieri S" first="Sandra E" last="Staffieri">Sandra E. Staffieri</name><affiliation><nlm:aff id="A13">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia</nlm:aff></affiliation></author><author><name sortKey="Teo, Yik Ying" sort="Teo, Yik Ying" uniqKey="Teo Y" first="Yik-Ying" last="Teo">Yik-Ying Teo</name><affiliation><nlm:aff id="A4">Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A24">Department of Statistics and Applied Probability, National University of Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Cuellar Partida, Gabriel" sort="Cuellar Partida, Gabriel" uniqKey="Cuellar Partida G" first="Gabriel" last="Cuellar-Partida">Gabriel Cuellar-Partida</name><affiliation><nlm:aff id="A8">Statistical Genetics, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Australia 4029</nlm:aff></affiliation></author><author><name sortKey="Luo, Xiaoyan" sort="Luo, Xiaoyan" uniqKey="Luo X" first="Xiaoyan" last="Luo">Xiaoyan Luo</name><affiliation><nlm:aff id="A25">Duke University, Duke Eye Center, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Allingham, R Rand" sort="Allingham, R Rand" uniqKey="Allingham R" first="R Rand" last="Allingham">R Rand Allingham</name><affiliation><nlm:aff id="A26">Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Richards, Julia E" sort="Richards, Julia E" uniqKey="Richards J" first="Julia E" last="Richards">Julia E. Richards</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Senft, Andrea" sort="Senft, Andrea" uniqKey="Senft A" first="Andrea" last="Senft">Andrea Senft</name><affiliation><nlm:aff id="A27">Institute of Medical Biometry and Statistics, University Hospital Schleswig-Holstein, Lübeck, Germany</nlm:aff></affiliation></author><author><name sortKey="Karssen, Lennart C" sort="Karssen, Lennart C" uniqKey="Karssen L" first="Lennart C" last="Karssen">Lennart C. Karssen</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zheng, Yingfeng" sort="Zheng, Yingfeng" uniqKey="Zheng Y" first="Yingfeng" last="Zheng">Yingfeng Zheng</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation></author><author><name sortKey="Bellenguez, Celine" sort="Bellenguez, Celine" uniqKey="Bellenguez C" first="Céline" last="Bellenguez">Céline Bellenguez</name><affiliation><nlm:aff id="A28">Inserm, UMR774, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Université Lille 2, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Institut Pasteur de Lille, France</nlm:aff></affiliation></author><author><name sortKey="Xu, Liang" sort="Xu, Liang" uniqKey="Xu L" first="Liang" last="Xu">Liang Xu</name><affiliation><nlm:aff id="A19">Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China 100730</nlm:aff></affiliation></author><author><name sortKey="Iglesias, Adriana I" sort="Iglesias, Adriana I" uniqKey="Iglesias A" first="Adriana I" last="Iglesias">Adriana I. Iglesias</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wilson, James F" sort="Wilson, James F" uniqKey="Wilson J" first="James F" last="Wilson">James F. Wilson</name><affiliation><nlm:aff id="A31">Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Kang, Jae H" sort="Kang, Jae H" uniqKey="Kang J" first="Jae H" last="Kang">Jae H. Kang</name><affiliation><nlm:aff id="A32">Channing Division of Network Medicine, Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Van Leeuwen, Elisabeth M" sort="Van Leeuwen, Elisabeth M" uniqKey="Van Leeuwen E" first="Elisabeth M" last="Van Leeuwen">Elisabeth M. Van Leeuwen</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Jonsson, Vesteinn" sort="Jonsson, Vesteinn" uniqKey="Jonsson V" first="Vesteinn" last="Jonsson">Vesteinn Jonsson</name><affiliation><nlm:aff id="A33">Department of Ophthalmology, Landspitali National University Hospital, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Thorsteinsdottir, Unnur" sort="Thorsteinsdottir, Unnur" uniqKey="Thorsteinsdottir U" first="Unnur" last="Thorsteinsdottir">Unnur Thorsteinsdottir</name><affiliation><nlm:aff id="A16">deCODE/Amgen, 101 Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Despriet, Dominiek D G" sort="Despriet, Dominiek D G" uniqKey="Despriet D" first="Dominiek D. G." last="Despriet">Dominiek D. G. Despriet</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ennis, Sarah" sort="Ennis, Sarah" uniqKey="Ennis S" first="Sarah" last="Ennis">Sarah Ennis</name><affiliation><nlm:aff id="A34">Human Genetics & Genomic Medicine, Faulty of Medicine, University of Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Moroi, Sayoko E" sort="Moroi, Sayoko E" uniqKey="Moroi S" first="Sayoko E" last="Moroi">Sayoko E. Moroi</name><affiliation><nlm:aff id="A35">Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G" last="Martin">Nicholas G. Martin</name><affiliation><nlm:aff id="A36">Genetic Epidemiology, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Jansonius, Nomdo M" sort="Jansonius, Nomdo M" uniqKey="Jansonius N" first="Nomdo M" last="Jansonius">Nomdo M. Jansonius</name><affiliation><nlm:aff id="A37">Department of Ophthalmology, University Medical Center Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Yazar, Seyhan" sort="Yazar, Seyhan" uniqKey="Yazar S" first="Seyhan" last="Yazar">Seyhan Yazar</name><affiliation><nlm:aff id="A38">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.</nlm:aff></affiliation></author><author><name sortKey="Tai, E Shyong" sort="Tai, E Shyong" uniqKey="Tai E" first="E-Shyong" last="Tai">E-Shyong Tai</name><affiliation><nlm:aff id="A4">Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Duke-National University of Singapore, Graduate Medical School, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Medicine, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation></author><author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name><affiliation><nlm:aff id="A27">Institute of Medical Biometry and Statistics, University Hospital Schleswig-Holstein, Lübeck, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Inserm, UMR774, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Université Lille 2, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A40">Centre Hospitalier Régional Universitaire de Lille, France</nlm:aff></affiliation></author><author><name sortKey="Kirwan, James" sort="Kirwan, James" uniqKey="Kirwan J" first="James" last="Kirwan">James Kirwan</name><affiliation><nlm:aff id="A41">Department of Ophthalmology, Portsmouth Hospitals NHS Trust, Portsmouth, UK</nlm:aff></affiliation></author><author><name sortKey="Van Koolwijk, Leonieke M E" sort="Van Koolwijk, Leonieke M E" uniqKey="Van Koolwijk L" first="Leonieke M. E." last="Van Koolwijk">Leonieke M. E. Van Koolwijk</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael A" last="Hauser">Michael A. Hauser</name><affiliation><nlm:aff id="A26">Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A42">Department of Medicine, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Jonasson, Fridbert" sort="Jonasson, Fridbert" uniqKey="Jonasson F" first="Fridbert" last="Jonasson">Fridbert Jonasson</name><affiliation><nlm:aff id="A43">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Leo, Paul" sort="Leo, Paul" uniqKey="Leo P" first="Paul" last="Leo">Paul Leo</name><affiliation><nlm:aff id="A44">The University of Queensland, Diamantina Institute, Woollongabba, Australia</nlm:aff></affiliation></author><author><name sortKey="Loomis, Stephanie J" sort="Loomis, Stephanie J" uniqKey="Loomis S" first="Stephanie J" last="Loomis">Stephanie J. Loomis</name><affiliation><nlm:aff id="A45">Dept. Ophthalmology Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Fogarty, Rhys" sort="Fogarty, Rhys" uniqKey="Fogarty R" first="Rhys" last="Fogarty">Rhys Fogarty</name><affiliation><nlm:aff id="A46">Department of Ophthalmology, Flinders University, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Kearns, Lisa" sort="Kearns, Lisa" uniqKey="Kearns L" first="Lisa" last="Kearns">Lisa Kearns</name><affiliation><nlm:aff id="A13">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia</nlm:aff></affiliation></author><author><name sortKey="Lackner, Karl J" sort="Lackner, Karl J" uniqKey="Lackner K" first="Karl J" last="Lackner">Karl J. Lackner</name><affiliation><nlm:aff id="A49">Institute of Clinical Chemistry and Laboratory Medicine, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="De Jong, Paulus T V M" sort="De Jong, Paulus T V M" uniqKey="De Jong P" first="Paulus T. V. M." last="De Jong">Paulus T. V. M. De Jong</name><affiliation><nlm:aff id="A50">Netherlands Institute for Neuroscience, Amsterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A51">Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A52">Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Simpson, Claire L" sort="Simpson, Claire L" uniqKey="Simpson C" first="Claire L" last="Simpson">Claire L. Simpson</name><affiliation><nlm:aff id="A11">National Human Genome Research Institute, National Institutes of Health, Baltimore, MD 21224, USA</nlm:aff></affiliation></author><author><name sortKey="Pennell, Craig E" sort="Pennell, Craig E" uniqKey="Pennell C" first="Craig E" last="Pennell">Craig E. Pennell</name><affiliation><nlm:aff id="A53">School of Women’s and Infants’ Health, The University of Western Australia, Perth, Australia</nlm:aff></affiliation></author><author><name sortKey="Oostra, Ben A" sort="Oostra, Ben A" uniqKey="Oostra B" first="Ben A" last="Oostra">Ben A. Oostra</name><affiliation><nlm:aff id="A54">Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G" last="Uitterlinden">André G. Uitterlinden</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Saw, Seang Mei" sort="Saw, Seang Mei" uniqKey="Saw S" first="Seang-Mei" last="Saw">Seang-Mei Saw</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Duke-National University of Singapore, Graduate Medical School, Singapore</nlm:aff></affiliation></author><author><name sortKey="Lotery, Andrew J" sort="Lotery, Andrew J" uniqKey="Lotery A" first="Andrew J" last="Lotery">Andrew J. Lotery</name><affiliation><nlm:aff id="A55">Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Bailey Wilson, Joan E" sort="Bailey Wilson, Joan E" uniqKey="Bailey Wilson J" first="Joan E" last="Bailey-Wilson">Joan E. Bailey-Wilson</name><affiliation><nlm:aff id="A11">National Human Genome Research Institute, National Institutes of Health, Baltimore, MD 21224, USA</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vingerling, Johannes R" sort="Vingerling, Johannes R" uniqKey="Vingerling J" first="Johannes R" last="Vingerling">Johannes R. Vingerling</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Maubaret, Cecilia" sort="Maubaret, Cecilia" uniqKey="Maubaret C" first="Cécilia" last="Maubaret">Cécilia Maubaret</name><affiliation><nlm:aff id="A56">Univ. Bordeaux, ISPED, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A57">Inserm, Centre INSERM U897-Epidemiologie-Biostatistique Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Pfeiffer, Norbert" sort="Pfeiffer, Norbert" uniqKey="Pfeiffer N" first="Norbert" last="Pfeiffer">Norbert Pfeiffer</name><affiliation><nlm:aff id="A14">Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="Wolfs, Roger C W" sort="Wolfs, Roger C W" uniqKey="Wolfs R" first="Roger C. W." last="Wolfs">Roger C. W. Wolfs</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Lemij, Hans G" sort="Lemij, Hans G" uniqKey="Lemij H" first="Hans G" last="Lemij">Hans G. Lemij</name><affiliation><nlm:aff id="A58">Glaucoma Service, the Rotterdam Eye Hospital, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Young, Terri L" sort="Young, Terri L" uniqKey="Young T" first="Terri L" last="Young">Terri L. Young</name><affiliation><nlm:aff id="A25">Duke University, Duke Eye Center, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Pasquale, Louis R" sort="Pasquale, Louis R" uniqKey="Pasquale L" first="Louis R" last="Pasquale">Louis R. Pasquale</name><affiliation><nlm:aff id="A32">Channing Division of Network Medicine, Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A45">Dept. Ophthalmology Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Delcourt, Cecile" sort="Delcourt, Cecile" uniqKey="Delcourt C" first="Cécile" last="Delcourt">Cécile Delcourt</name><affiliation><nlm:aff id="A56">Univ. Bordeaux, ISPED, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A57">Inserm, Centre INSERM U897-Epidemiologie-Biostatistique Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Spector, Timothy D" sort="Spector, Timothy D" uniqKey="Spector T" first="Timothy D" last="Spector">Timothy D. Spector</name><affiliation><nlm:aff id="A1">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Klaver, Caroline C W" sort="Klaver, Caroline C W" uniqKey="Klaver C" first="Caroline C. W." last="Klaver">Caroline C. W. Klaver</name><affiliation><nlm:aff id="A6">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Small, Kerrin S" sort="Small, Kerrin S" uniqKey="Small K" first="Kerrin S" last="Small">Kerrin S. Small</name><affiliation><nlm:aff id="A1">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Burdon, Kathryn P" sort="Burdon, Kathryn P" uniqKey="Burdon K" first="Kathryn P" last="Burdon">Kathryn P. Burdon</name><affiliation><nlm:aff id="A46">Department of Ophthalmology, Flinders University, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation><nlm:aff id="A16">deCODE/Amgen, 101 Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Wong, Tien Yin" sort="Wong, Tien Yin" uniqKey="Wong T" first="Tien-Yin" last="Wong">Tien-Yin Wong</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation></author><author><name sortKey="Viswanathan, Ananth" sort="Viswanathan, Ananth" uniqKey="Viswanathan A" first="Ananth" last="Viswanathan">Ananth Viswanathan</name><affiliation><nlm:aff id="A60">NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Mackey, David A" sort="Mackey, David A" uniqKey="Mackey D" first="David A" last="Mackey">David A. Mackey</name><affiliation><nlm:aff id="A13">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A38">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.</nlm:aff></affiliation></author><author><name sortKey="Craig, Jamie E" sort="Craig, Jamie E" uniqKey="Craig J" first="Jamie E" last="Craig">Jamie E. Craig</name><affiliation><nlm:aff id="A46">Department of Ophthalmology, Flinders University, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Wiggs, Janey L" sort="Wiggs, Janey L" uniqKey="Wiggs J" first="Janey L" last="Wiggs">Janey L. Wiggs</name><affiliation><nlm:aff id="A45">Dept. Ophthalmology Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M" last="Van Duijn">Cornelia M. Van Duijn</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Hammond, Christopher J" sort="Hammond, Christopher J" uniqKey="Hammond C" first="Christopher J" last="Hammond">Christopher J. Hammond</name><affiliation><nlm:aff id="A1">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Aung, Tin" sort="Aung, Tin" uniqKey="Aung T" first="Tin" last="Aung">Tin Aung</name><affiliation><nlm:aff id="A2">Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</nlm:aff></affiliation></author></analytic><series><title level="j">Nature genetics</title><idno type="ISSN">1061-4036</idno><idno type="eISSN">1546-1718</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P3">Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma and IOP variability may herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multiethnic participants for IOP. We confirm genetic association of known loci for IOP and primary open angle glaucoma (POAG) and identify four new IOP loci located on chromosome 3q25.31 within the <italic>FNDC3B</italic> gene (p=4.19×10<sup>−08</sup> for rs6445055), two on chromosome 9 (p=2.80×10<sup>−11</sup> for rs2472493 near <italic>ABCA1</italic> and p=6.39×10<sup>−11</sup> for rs8176693 within <italic>ABO</italic>) and one on chromosome 11p11.2 (best p=1.04×10<sup>−11</sup> for rs747782). Separate meta-analyses of four independent POAG cohorts, totaling 4,284 cases and 95,560 controls, show that three of these IOP loci are also associated with POAG.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Quigley, Ha" uniqKey="Quigley H">HA Quigley</name></author><author><name sortKey="Broman, At" uniqKey="Broman A">AT Broman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heijl, A" uniqKey="Heijl A">A Heijl</name></author><author><name sortKey="Leske, Mc" uniqKey="Leske M">MC Leske</name></author><author><name sortKey="Bengtsson, B" uniqKey="Bengtsson B">B Bengtsson</name></author><author><name sortKey="Hyman, L" uniqKey="Hyman L">L Hyman</name></author><author><name sortKey="Hussein, M" uniqKey="Hussein M">M Hussein</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kass, Ma" uniqKey="Kass M">MA 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Genet.</journal-id><journal-title-group><journal-title>Nature genetics</journal-title></journal-title-group><issn pub-type="ppub">1061-4036</issn><issn pub-type="epub">1546-1718</issn></journal-meta><article-meta><article-id pub-id-type="pmid">25173106</article-id><article-id pub-id-type="pmc">4177225</article-id><article-id pub-id-type="doi">10.1038/ng.3087</article-id><article-id pub-id-type="manuscript">EMS59965</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Genome-wide analysis of multiethnic cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Hysi</surname><given-names>Pirro G</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" 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ref-type="aff" rid="A59">59</xref></contrib><contrib contrib-type="author"><collab>Wellcome Trust Case Control Consortium 2</collab><xref ref-type="aff" rid="A59">59</xref></contrib><contrib contrib-type="author"><name><surname>Viswanathan</surname><given-names>Ananth</given-names></name><xref ref-type="author-notes" rid="FN1">**</xref><xref ref-type="aff" rid="A60">60</xref></contrib><contrib contrib-type="author"><name><surname>Mackey</surname><given-names>David A</given-names></name><xref ref-type="author-notes" rid="FN1">**</xref><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A38">38</xref></contrib><contrib contrib-type="author"><name><surname>Craig</surname><given-names>Jamie E</given-names></name><xref ref-type="author-notes" rid="FN1">**</xref><xref ref-type="aff" rid="A46">46</xref></contrib><contrib contrib-type="author"><name><surname>Wiggs</surname><given-names>Janey L</given-names></name><xref ref-type="author-notes" rid="FN1">**</xref><xref ref-type="aff" rid="A45">45</xref></contrib><contrib contrib-type="author"><name><surname>van Duijn</surname><given-names>Cornelia M</given-names></name><xref ref-type="author-notes" rid="FN1">**</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Hammond</surname><given-names>Christopher J</given-names></name><xref ref-type="author-notes" rid="FN1">**</xref><xref ref-type="aff" rid="A1">1</xref><xref ref-type="corresp" rid="CR1">‡</xref></contrib><contrib contrib-type="author"><name><surname>Aung</surname><given-names>Tin</given-names></name><xref ref-type="author-notes" rid="FN1">**</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="corresp" rid="CR1">‡</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Twin Research and Genetic Epidemiology, King’s College London, UK</aff><aff id="A2"><label>2</label>Singapore Eye Research Institute, Singapore National Eye Centre, Singapore</aff><aff id="A3"><label>3</label>Department of Ophthalmology, National University of Singapore and National University Health System, Singapore</aff><aff id="A4"><label>4</label>Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore</aff><aff id="A5"><label>5</label>Duke-National University of Singapore, Graduate Medical School, Singapore</aff><aff id="A6"><label>6</label>Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</aff><aff id="A7"><label>7</label>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</aff><aff id="A8"><label>8</label>Statistical Genetics, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Australia 4029</aff><aff id="A9"><label>9</label>Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA</aff><aff id="A10"><label>10</label>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health and, Baltimore, MD, USA</aff><aff id="A11"><label>11</label>National Human Genome Research Institute, National Institutes of Health, Baltimore, MD 21224, USA</aff><aff id="A12"><label>12</label>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh</aff><aff id="A13"><label>13</label>Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia</aff><aff id="A14"><label>14</label>Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany</aff><aff id="A15"><label>15</label>Institute of Ophthalmology, University College London, UK</aff><aff id="A16"><label>16</label>deCODE/Amgen, 101 Reykjavik, Iceland</aff><aff id="A17"><label>17</label>Division of Human Genetics, Genome Institute of Singapore, Singapore</aff><aff id="A18"><label>18</label>Eye Clinic, 105 Reykjavik, Iceland</aff><aff id="A19"><label>19</label>Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China 100730</aff><aff id="A20"><label>20</label>Department of Internal Medicine II, University Medical Center Mainz, Mainz, Germany</aff><aff id="A21"><label>21</label>Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA</aff><aff id="A22"><label>22</label>NHS Princess Alexandra Eye Pavilion, Edinburgh, UK</aff><aff id="A23"><label>23</label>Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Germany</aff><aff id="A24"><label>24</label>Department of Statistics and Applied Probability, National University of Singapore, Singapore</aff><aff id="A25"><label>25</label>Duke University, Duke Eye Center, Durham, NC, USA</aff><aff id="A26"><label>26</label>Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA</aff><aff id="A27"><label>27</label>Institute of Medical Biometry and Statistics, University Hospital Schleswig-Holstein, Lübeck, Germany</aff><aff id="A28"><label>28</label>Inserm, UMR774, Lille, France</aff><aff id="A29"><label>29</label>Université Lille 2, Lille, France</aff><aff id="A30"><label>30</label>Institut Pasteur de Lille, France</aff><aff id="A31"><label>31</label>Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, UK</aff><aff id="A32"><label>32</label>Channing Division of Network Medicine, Harvard Medical School, Boston, MA, USA</aff><aff id="A33"><label>33</label>Department of Ophthalmology, Landspitali National University Hospital, Reykjavik, Iceland</aff><aff id="A34"><label>34</label>Human Genetics & Genomic Medicine, Faulty of Medicine, University of Southampton, UK</aff><aff id="A35"><label>35</label>Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA</aff><aff id="A36"><label>36</label>Genetic Epidemiology, QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, Brisbane, Australia</aff><aff id="A37"><label>37</label>Department of Ophthalmology, University Medical Center Groningen, the Netherlands</aff><aff id="A38"><label>38</label>Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.</aff><aff id="A39"><label>39</label>Department of Medicine, National University of Singapore and National University Health System, Singapore</aff><aff id="A40"><label>40</label>Centre Hospitalier Régional Universitaire de Lille, France</aff><aff id="A41"><label>41</label>Department of Ophthalmology, Portsmouth Hospitals NHS Trust, Portsmouth, UK</aff><aff id="A42"><label>42</label>Department of Medicine, Duke University Medical Center, Durham, NC, USA</aff><aff id="A43"><label>43</label>Faculty of Medicine, University of Iceland, Reykjavik, Iceland</aff><aff id="A44"><label>44</label>The University of Queensland, Diamantina Institute, Woollongabba, Australia</aff><aff id="A45"><label>45</label>Dept. Ophthalmology Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA, USA</aff><aff id="A46"><label>46</label>Department of Ophthalmology, Flinders University, Adelaide, Australia</aff><aff id="A47"><label>47</label>Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands</aff><aff id="A48"><label>48</label>Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, the Netherlands</aff><aff id="A49"><label>49</label>Institute of Clinical Chemistry and Laboratory Medicine, Mainz, Germany</aff><aff id="A50"><label>50</label>Netherlands Institute for Neuroscience, Amsterdam, the Netherlands</aff><aff id="A51"><label>51</label>Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands</aff><aff id="A52"><label>52</label>Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands</aff><aff id="A53"><label>53</label>School of Women’s and Infants’ Health, The University of Western Australia, Perth, Australia</aff><aff id="A54"><label>54</label>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands</aff><aff id="A55"><label>55</label>Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK</aff><aff id="A56"><label>56</label>Univ. Bordeaux, ISPED, Bordeaux, France</aff><aff id="A57"><label>57</label>Inserm, Centre INSERM U897-Epidemiologie-Biostatistique Bordeaux, France</aff><aff id="A58"><label>58</label>Glaucoma Service, the Rotterdam Eye Hospital, Rotterdam, the Netherlands</aff><aff id="A59"><label>59</label>The full list of collaborators participating in these consortia is in the<xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref></aff><aff id="A60"><label>60</label>NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK</aff><author-notes><fn id="FN2"><p id="P1"><bold>AUTHOR CONTRIBUTIONS:</bold> P.G.H., C-Y.C., H.S., S.M., J.N.CB and R.W. performed analyses and drafted the manuscript; S.M., A.J.L., J.E.B-W., V.V., L.R.P., N.P., C.D., A.V., D.A.M., J.E.C., J.L.W., C.M.vD., C.J.H. and T.A. jointly conceived the project and supervised the work; P.G.H, H.S., R.W., A.N., A.W.H., A.M., C.V., R.H., G.T., B.A.O., S-M.S., W.D.R., E.V., C-C.K., D.D.G.D., J.L., J.L.H., Y.X.W., F.R., P.S.W., H.G.L., A.B.O., J.Z.L., B.W.F., R.C.W.W., T.Z., S.E.S., Y-Y.T., G.C-P, X.L., RR.A., J.E.R., A.S., Y.Z., C.B., A.I.I., L.X., J.F.W., J.H.K., L.C.K., K.S., V.J., A.G.U., N.M.J., U.T., J.R.V., N.A., S.E., S.E.M., N.G.M., S.Y., E-S.T., E.M.Vl., P.A., J.K., M.A.H., F.J., P.L., A.H., S.J.L., R.F., L.K., P.T.V.M.Dj., K.J.L., C.L.S., C.E.P., L.M.E.vK., C.M., C.C.W.K., K.P.B., T.D.S., T-Y.W., D.A.M., J.E.C. and A.B.S. were responsible for cohort-specific activities, data generation and analyses; T.L.Y. and K.S.S. responsible for expression and eQTL work; P.G.H., C-Y.C., H.S., S.M., T-Y.W., D.A.M., J.L.W., C.M.vD. and C.J.H. critically reviewed the manuscript.</p></fn><fn id="FN1"><label>**</label><p id="P2">These authors jointly directed this work</p></fn><corresp id="CR1"><label>‡</label>Correspondence should be addressed to <email>aung_tin@yahoo.co.uk</email> or <email>chris.hammond@kcl.ac.uk</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>12</day><month>8</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>31</day><month>8</month><year>2014</year></pub-date><pub-date pub-type="ppub"><month>10</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>4</month><year>2015</year></pub-date><volume>46</volume><issue>10</issue><fpage>1126</fpage><lpage>1130</lpage><pmc-comment>elocation-id from pubmed: 10.1038/ng.3087</pmc-comment>
<permissions><license><license-p>Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:<uri xlink:type="simple" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</uri></license-p></license></permissions><abstract><p id="P3">Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma and IOP variability may herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multiethnic participants for IOP. We confirm genetic association of known loci for IOP and primary open angle glaucoma (POAG) and identify four new IOP loci located on chromosome 3q25.31 within the <italic>FNDC3B</italic> gene (p=4.19×10<sup>−08</sup> for rs6445055), two on chromosome 9 (p=2.80×10<sup>−11</sup> for rs2472493 near <italic>ABCA1</italic> and p=6.39×10<sup>−11</sup> for rs8176693 within <italic>ABO</italic>) and one on chromosome 11p11.2 (best p=1.04×10<sup>−11</sup> for rs747782). Separate meta-analyses of four independent POAG cohorts, totaling 4,284 cases and 95,560 controls, show that three of these IOP loci are also associated with POAG.</p></abstract></article-meta></front><body><p id="P4">Primary open angle glaucoma (POAG) is the leading cause of irreversible blindness in the world<sup><xref rid="R1" ref-type="bibr">1</xref></sup>. The only modifiable risk factor for the development and progression of glaucoma is high intraocular pressure (IOP)<sup><xref rid="R2" ref-type="bibr">2</xref></sup>, and lowering IOP is currently the only therapy that can reduce glaucomatous progression, even in forms of glaucoma that have IOP close to the statistical norm for the population (normal tension glaucoma or NTG)<sup><xref rid="R3" ref-type="bibr">3</xref><xref rid="R4" ref-type="bibr">4</xref></sup>. POAG and IOP are highly heritable; the lifetime risk of developing POAG is 22% among first degree relatives of patients<sup><xref rid="R5" ref-type="bibr">5</xref></sup>, which is approximately 10 times higher than the rest of the population<sup><xref rid="R1" ref-type="bibr">1</xref></sup>. The IOP heritability is estimated to be approximately 55%<sup><xref rid="R6" ref-type="bibr">6</xref></sup>. Genetic studies have shown that the genetic risk of POAG and IOP are partly shared; polymorphisms within the <italic>TMCO1</italic> gene are associated with both POAG risk <sup><xref rid="R7" ref-type="bibr">7</xref></sup> and IOP<sup><xref rid="R8" ref-type="bibr">8</xref></sup>. Studying genetic determinants of IOP is therefore likely to provide critical insights into the genetic architecture of POAG and open new avenues for therapeutic intervention.</p><p id="P5">In this study we present results from a meta-analysis of genome-wide association studies (GWAS) of IOP from 18 studies participating in the International Glaucoma Genetics Consortium (IGGC) and an assessment of the importance of the genetic findings for susceptibility to POAG (<xref ref-type="fig" rid="F1">Figure 1</xref>). The IOP meta-analysis included 35,296 subjects (7,738 Asians and 27,558 of European descent) drawn from the general populations of seven countries. Demographic characteristics of these population cohorts are given in the <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1</xref>. Genotyping assays and imputation to HapMap2 haplotypes were performed at individual sites. Association analyses were performed using an additive model, with IOP as outcome, number of alleles at each polymorphic site as predictors, adjusting for age and sex. IOP levels for participants who were receiving IOP-lowering therapy at the time of the study and whose baseline, pre-treatment levels were not available were imputed as previously described<sup><xref rid="R8" ref-type="bibr">8</xref></sup>. Subjects who had undergone surgery or had other eye diseases that could affect IOP were removed (<xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>). Secondary analyses were carried out adjusting for central corneal thickness (CCT), which is known to influence IOP measurements <sup><xref rid="R9" ref-type="bibr">9</xref></sup>.</p><p id="P6">After applying conventional quality control filters, a fixed effects meta-analysis of 22 autosomes across the cohorts was performed with approximately 2.5 million markers. Within-study genomic inflation factors<sup><xref rid="R10" ref-type="bibr">10</xref></sup> ranged between 0.992 and 1.043 (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 2</xref> and <xref ref-type="supplementary-material" rid="SD1">Supplementary Figure 1</xref>), indicating a lack of major population stratification bias within each study. SNPs available in fewer than 16 cohorts or showing large heterogeneity (defined as I<sup>2</sup>>75% <sup><xref rid="R11" ref-type="bibr">11</xref></sup>) were removed. We found 145 SNPs (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 3</xref>) whose association crossed the conventional genome-wide significance threshold (p<5×10<sup>−08</sup>) <sup><xref rid="R12" ref-type="bibr">12</xref></sup>. All of these SNPs clustered around seven separate regions of the genome (<xref ref-type="fig" rid="F2">Figure 2</xref>, <xref ref-type="supplementary-material" rid="SD1">Supplementary Figures 2</xref> and <xref ref-type="supplementary-material" rid="SD1">3</xref>). Two of the regions associated with IOP in our meta-analysis had previously been implicated in IOP variability: the region near the <italic>TMCO1</italic> locus<sup><xref rid="R7" ref-type="bibr">7</xref>,<xref rid="R8" ref-type="bibr">8</xref></sup> (p=2.19×10<sup>−09</sup> for rs7555523), and near <italic>GAS7</italic> gene<sup><xref rid="R8" ref-type="bibr">8</xref></sup> (p=1.03×10<sup>−11</sup> for rs9913911). A third locus, novel for IOP, was near the <italic>CAV1</italic> and <italic>CAV2</italic> genes (p=1.87×10<sup>−11</sup> for rs10258482) which had previously been associated with POAG<sup><xref rid="R13" ref-type="bibr">13</xref></sup>.</p><p id="P7">Novel associations were identified within large linkage disequilibrium (LD) block on chromosome 11 encompassing, among other genes, <italic>AGBL2</italic>, <italic>SPI1</italic> and <italic>PTPRJ</italic> (best p=1.04×10<sup>−11</sup> for rs747782), (<xref ref-type="supplementary-material" rid="SD1">Supplementary Figure 1</xref>). Two additional loci were mapped on chromosome 9: one at 9q31.1 upstream the <italic>ABCA1</italic> gene (p=2.80×10<sup>−11</sup> for rs2472493) and the other at 9q34.2 within the <italic>ABO</italic> blood group gene (p=3.08×10<sup>−11</sup> for rs8176743). A fourth region was detected on chr3q25.31, within the <italic>FNDC3B</italic> gene (p=4.19×10<sup>−08</sup> for rs6445055).</p><p id="P8">Interestingly, of all the loci previously associated with glaucoma or related quantitative traits<sup><xref rid="R14" ref-type="bibr">14</xref></sup>, CDKN2BAS and SIX1/SIX6 are not associated with IOP in the meta-analysis. It is possible these two loci exert their influence on POAG through mechanisms unrelated to intraocular pressure.</p><p id="P9">Genome-wide significant SNPs from the IOP meta-analysis were then investigated for their effect on the clinical outcome of POAG in four independent cohorts representing a combined 4,284 POAG cases (normal and high tension glaucoma) and 95,560 controls (details about these cohorts in the <xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>). Associations to POAG were found for the novel regions near <italic>ABCA1</italic> gene (p=4.15×10<sup>−09</sup> for rs2472493), near the <italic>FNDC3B</italic> gene (p=0.03 for rs6445055) and on the chromosome 11 cluster (p=0.008 for rs12419342). We did not find significant statistical evidence of association of POAG to the <italic>ABO</italic> locus. The case-control analyses reinforced association evidence at the previously identified loci on <italic>TMCO1</italic> (p=1.34×10<sup>−16</sup> for rs7555523), <italic>CAV1/CAV2</italic> (p=6.27×10<sup>−09</sup> for rs10258482) and <italic>GAS7</italic> (p=5.22×10<sup>−13</sup> for rs12150284). All alleles associated with increased IOP levels also raised glaucoma risk (<xref ref-type="table" rid="T1">Table 1</xref>).</p><p id="P10">We then examined whether the effect sizes of SNPs on IOP levels (Beta<sub>IOP</sub>) were linearly related to their effect sizes on POAG (Beta<sub>POAG</sub>) using a causal inference framework as previously described<sup><xref rid="R15" ref-type="bibr">15</xref></sup>. In a linear regression analysis, we observed a significant association between Beta<sub>IOP</sub> and Beta<sub>POAG</sub> (p=0.03, <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 4</xref>), suggesting the strength of SNPs’ effect on IOP levels is correlated with their effects on the risk of POAG.</p><p id="P11">We subsequently investigated the relationship between variants within the seven regions associated with IOP and <italic>cis</italic>- regulation of mRNA expression in three tissues (adipose, lymphoblastoid cell lines [LCLs] and skin) from a sample of 856 British subjects<sup><xref rid="R16" ref-type="bibr">16</xref></sup>. The most significant eQTL associations were generally observed in LCLs for most loci, except for CAV1 where effects were strongest in adipose and skin tissues (<xref ref-type="table" rid="T2">Table 2</xref>). Significant eQTL association was observed for rs4656461 and rs7555523 (p=0.003 and p=0.0001 with <italic>TMCO1</italic> and <italic>ALDH9A1</italic> transcript expressions in skin and LCLs respectively), rs2024211 (p=5.43×10<sup>−16</sup> and 3.84×10<sup>−13</sup> with <italic>CAV1</italic> in adipose and skin tissues respectively), rs2472493 with <italic>ABCA1</italic> (p=3.67×10<sup>−05</sup> in LCLs) and rs1681630 with the SPI1 expression on chromosome 11 (p=2.72×10<sup>−10</sup> in LCLs) among others (<xref ref-type="table" rid="T2">Table 2</xref>, <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 5A</xref>). These SNPs also had the strongest eQTL effects for their respective transcripts (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 5B</xref>).</p><p id="P12">We measured the mRNA expression levels of the identified genes in adult ocular tissues using reverse-transcriptase PCR. We found that most of the identified genes, including <italic>TMCO1, FDNC3B, CAV1/CAV2, ABCA1</italic> and <italic>GAS7</italic> were expressed in most ocular tissues (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 6</xref>). The expression of genes within the chromosome 11 locus showed varied expression levels across ocular tissues.</p><p id="P13">Gene-based tests or Gene Ontology enrichment analyses failed to identify any new genes or pathways after multiple testing correction (<xref ref-type="supplementary-material" rid="SD1">Supplementary Tables 7</xref> and <xref ref-type="supplementary-material" rid="SD1">8</xref>).</p><p id="P14">Altogether, these SNPs explain approximately 1.2% of the IOP heritability in the TwinsUK cohort<sup><xref rid="R17" ref-type="bibr">17</xref></sup>, 1.5% of the IOP phenotypic variability in the Rotterdam study<sup><xref rid="R18" ref-type="bibr">18</xref></sup> and between 0.6 and 1.2% in Asians. <italic>FNDC3B</italic> has been associated with central corneal thickness (CCT) <sup><xref rid="R19" ref-type="bibr">19</xref></sup> and as CCT has a significant effect on IOP measurements<sup><xref rid="R20" ref-type="bibr">20</xref></sup>, we performed an additional meta-analysis of IOP adjusted for age, sex and CCT in a smaller subsample which had CCT measures (19,563 subjects from 13 population cohorts). The association for rs6445055 remained nominally significant, albeit reduced (p= 9.87×10<sup>−04</sup>, β= −0.121 compared to −0.177 prior to adjustment for CCT). This suggests that this locus has at least some CCT-independent effect over the IOP levels. The association evidence remained consistent, although slightly reduced, for the other loci (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 9</xref>).</p><p id="P15">We report association of variants within the <italic>ABCA1</italic> gene and IOP and POAG. A strong eQTL effect was observed in LCLs (p=3.67×10<sup>−05</sup>) for the most highly associated SNP (rs2472493) in our analyses. The <italic>ABCA1</italic> gene is expressed in many tissues<sup><xref rid="R21" ref-type="bibr">21</xref></sup> and its expression in leukocytes is significantly up-regulated in glaucoma patients<sup><xref rid="R22" ref-type="bibr">22</xref></sup>.</p><p id="P16">Associations for a number of SNPs within the <italic>ABO</italic> blood group gene and IOP, although statistically significant and homogeneous across the participating cohorts, were not observed in the glaucoma case-control meta-analysis. This might be due to type I error in the initial meta-analysis or insufficient power to detect a primarily IOP-led effect in cases that included NTG patients, resulting in a type II error in the latter. Four of the nine GWAS polymorphisms associated at genome-wide significance in the <italic>ABO</italic> locus are non-synonymous variants, determining B blood group<sup><xref rid="R23" ref-type="bibr">23</xref></sup>. This may be relevant given previous observations that the B blood group is epidemiologically associated with glaucoma, including POAG<sup><xref rid="R24" ref-type="bibr">24</xref></sup>, although the mechanisms remain unclear.</p><p id="P17">Association was found between IOP and variants lying over a large region on chromosome 11. Of the many genes in that region, eQTL analyses singled out <italic>SPI1</italic> and <italic>AGBL2</italic> as possible candidates for prioritization in future studies. eQTL analyses also raised the possibility of <italic>ALDH9A1</italic> as a candidate for IOP regulation, given its strong expression in ciliary body<sup><xref rid="R25" ref-type="bibr">25</xref></sup> and location just downstream of the <italic>TMCO1</italic>-associated variant. The eQTL results also suggest that <italic>CAV1</italic> is a stronger candidate than <italic>CAV2</italic>, although transcription regulation may not be the only mechanism influencing IOP at this locus.</p><p id="P18">Although IOP and POAG are strongly genetically correlated<sup><xref rid="R26" ref-type="bibr">26</xref></sup>, we explored further their shared genetic backgrounds. Using independent (i.e. not in LD) SNPs with p< 10<sup>−06</sup> in the IOP GWAS meta-analysis as described elsewhere<sup><xref rid="R27" ref-type="bibr">27</xref></sup>, we found a statistically significant polygenic overlap between IOP and POAG in the ANZRAG cohort (p=4.33×10<sup>−05</sup>). The variance explained in POAG was 0.7%, which changed little if less significant SNPs were progressively included in the model (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 10</xref>).</p><p id="P19">There are potential limitations to this study. First, there is variability across the studies in terms of IOP measurement methods, although the differences are likely to be small<sup><xref rid="R28" ref-type="bibr">28</xref></sup>. In addition, we maximized power to discover genetic variants of small effect size by including multiethnic cohorts, at the risk of introducing heterogeneity into the study. Heterogeneity was however generally low (<xref ref-type="table" rid="T1">Table 1</xref>) for most of the loci reported, so we consider our results to be conservative. Second, assessment of clinical importance using panels of POAG cases is not equivalent to a formal replication. Even in this case, we expect our results to be over-conservative at the price of reduced sensitivity, which could be a possible reason for non-validation of our association with IOP in the <italic>ABO</italic> blood group locus. Finally, we based our eQTL analysis on sample tissue availability rather than ideal ocular tissue types. Tissues such as trabecular meshwork would have been preferable, but they are impractical because they are generally less accessible. We tried to circumvent this limitation by studying three different tissues, but caution is required when interpreting eQTL results.</p><p id="P20">Despite these considerations, our report of seven loci associated with IOP and glaucoma, of which four are novel, is an important step forward to better understanding the mechanisms of IOP regulation-currently the only modifiable risk factor for POAG.</p><sec sec-type="methods" id="S1" specific-use="web-only"><title>Online Methods</title><sec sec-type="subjects" id="S2"><title>IGGC participants</title><p id="P21">All studies participating in this meta-analysis are part of the International Glaucoma Genetics Consortium. The discovery cohorts included 27,558 individuals of European ancestry from 14 studies (ALIENOR, BATS, BMES,<sup><xref rid="R29" ref-type="bibr">29</xref>,<xref rid="R30" ref-type="bibr">30</xref></sup> ERF,<sup><xref rid="R31" ref-type="bibr">31</xref>,<xref rid="R32" ref-type="bibr">32</xref></sup> Framingham Family Study,<sup><xref rid="R33" ref-type="bibr">33</xref></sup> GHS1, GHS2, ORCADES,<sup><xref rid="R34" ref-type="bibr">34</xref></sup> RAINE, <sup><xref rid="R35" ref-type="bibr">35</xref>-<xref rid="R37" ref-type="bibr">37</xref></sup> RS-I, RS-II, RS-III,<sup><xref rid="R38" ref-type="bibr">38</xref></sup> TEST<sup><xref rid="R39" ref-type="bibr">39</xref></sup> and TwinsUK<sup><xref rid="R40" ref-type="bibr">40</xref></sup>). In addition, 7,738 individuals of Asian ancestry from four cohorts (BES,<sup><xref rid="R41" ref-type="bibr">41</xref></sup> SCES,<sup><xref rid="R42" ref-type="bibr">42</xref></sup> SiMES,<sup><xref rid="R43" ref-type="bibr">43</xref></sup> SINDI,<sup><xref rid="R42" ref-type="bibr">42</xref></sup>) were included. In addition four case-control population panels were used, all of European ancestry: ANZRAG,<sup><xref rid="R7" ref-type="bibr">7</xref></sup> MEEI, NEIGHBOR and deCode. General methods, demographics and phenotyping of the study cohorts have previously been described extensively and are provided in the <xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref> and <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1</xref>. All studies were performed with the approval of their local Medical Ethics Committees and written informed consent was obtained from all participants in accordance with the Declaration of Helsinki.</p></sec><sec id="S3"><title>Phenotype measurements</title><p id="P22">Eligible participants underwent an ophthalmologic examination including measurements of IOP and, for most but not all studies, measurements of central corneal thickness (CCT). Each participating cohort was phenotyped separately and IOP measurement methods used by each are described in the <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1</xref>.</p></sec><sec id="S4"><title>Genotyping & imputation</title><p id="P23">The study samples were genotyped on either the Illumina (San Diego, CA, USA) or Affymetrix (Santa Clara, CA, USA) platforms. Each study performed single nucleotide polymorphism (SNP) imputation using the genotype data, together with the HapMap Phase II ethnically matched reference panels (CEU, JPT+CHB, or the 4 HapMap populations) on the basis of build 36 databases (release 22 or 24). The Markov Chain Haplotyping software, IMPUTE<sup><xref rid="R44" ref-type="bibr">44</xref>,<xref rid="R45" ref-type="bibr">45</xref></sup> or MACH,<sup><xref rid="R46" ref-type="bibr">46</xref></sup> were adopted for imputation. A detailed description regarding genotyping platforms and imputation procedures for each study is provided on <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1</xref>.</p><p id="P24">Stringent quality control of genotype data was applied in each cohort. Samples with low call rates (<95%) or with gender discrepancies were excluded. Cryptically related samples and outliers in population structure from principal component analyses were also excluded. SNPs flagged with missingness >5%, gross departure from Hardy Weinberg Equilibrium (<italic>P</italic> value <10<sup>−6</sup>) and minor allele frequency (MAF) <1% were removed from further analyses.</p></sec><sec id="S5"><title>Statistical Analysis</title><p id="P25">For each study, an allele-dosage regression model at each directly genotyped or imputed SNP was conducted to determine its association with IOP. Eyes with prior glaucoma surgery or laser were excluded. For subject receiving IOP-lowering medication, we added 25% to the measured IOP levels to estimate pre-treatment IOP, based on a reported average of 17% to 33% IOP reduction caused by IOP lowering medication in a meta-analysis of clinical trails.<sup><xref rid="R47" ref-type="bibr">47</xref></sup> The mean of the right and left IOP measurements was used. When data from only one eye were available, the IOP measurement from the available eye was used.</p><p id="P26">For the analyses, we assumed an additive genetic model where the dosage of each SNP is a continuous variable ranging from 0 to 2 for minor alleles carried. Primary analysis for IOP was adjusted for age and sex. Additional adjustment for principal components was carried out by a few participating cohorts to correct for subtle population substructure.</p><p id="P27">The per-SNP meta-analyses were performed using the GWAMA software with weighted inverse-variance approach, assuming fixed effects, as for initial discovery purposes the fixed-effects model is preferred for increased statistical power.<sup><xref rid="R48" ref-type="bibr">48</xref></sup> A Cochran’s Q test and <italic>I</italic><sup>2</sup> were used to assess heterogeneity across studies<sup><xref rid="R49" ref-type="bibr">49</xref></sup> . For each participating cohort, only SNPs with sufficient imputation quality scores (proper-info of IMPUTE or R<sup>2</sup> of MACH >0.3) were included into the meta-analysis.</p><p id="P28">Gene-based testing was conducted using VEGAS software<sup><xref rid="R50" ref-type="bibr">50</xref></sup> on the European ancestry and Asian ancestry meta-analysis results separately. VEGAS incorporates information from the full set of markers within a gene and accounts for LD between markers by using simulations from the multivariate normal distribution. For samples of European descent, we used the HapMap 2 CEU population as the reference to estimate patterns of LD. For Asian ancestry groups, we used the combined HapMap 2 JPT and CHB populations as the reference population to approximate LD patterns. To include gene regulatory regions, SNPs were included if they fell within 50 kb of a gene. We performed meta-analysis on the two sets of gene-based <italic>P</italic>-values using Fisher’s method.</p><p id="P29">VEGAS-Pathway analysis<sup><xref rid="R50" ref-type="bibr">50</xref>,<xref rid="R51" ref-type="bibr">51</xref></sup> was carried out using prespecified pathways from Gene Ontology. Pathways of with 10 to 1,000 components were selected, yielding 4,628 pathways. Pathway analysis was based on combining gene-based test results from VEGAS. Pathway <italic>P</italic>-values were computed by summing <italic>χ</italic><sup>2</sup> test statistics derived from VEGAS <italic>P</italic>-values. Empirical VEGAS-Pathway P values for each pathway were computed by comparing the summed <italic>χ</italic><sup>2</sup> test statistics from real data with those generated in 500,000 simulations where the relevant number (according to the size of the pathway) of randomly drawn <italic>χ</italic><sup>2</sup> test statistics was summed. To ensure that clusters of genes did not adversely affect results, within each pathway, gene sets were pruned such that each gene was >500 kb away from all other genes in the pathway. Where required, all but one of the clustered genes was dropped at random when genes were clustered. We performed meta-analysis on the two sets of pathway <italic>p</italic>-values using Fisher’s method.</p><p id="P30">To investigate shared genetic background by using a large number of autosomal SNPs we made a systematic evaluation of the overlap between the IOP and POAG based on profile scores following approaches previously described<sup><xref rid="R27" ref-type="bibr">27</xref></sup>. We estimated the relative risk for each SNP of interest based on a discovery set (IOP), with a profile score computed for every individual in a target set of interest (POAG). For each target set individual the profile score was computed as the number of risk alleles weighted by the effect size estimated in the discovery set. The discovery set comprised the European ancestry derived samples from our meta-analysis and the target set was was a set of 590 glaucoma cases and 3956 controls, as previously described<sup><xref rid="R7" ref-type="bibr">7</xref></sup>. To ensure that there was not a high degree of dependence between the SNPs included in the profile score, we filtered the set of SNPs used in the profile score so that only a set of 149,571 SNPs in low linkage disequilibrium (r<sup>2</sup><0.5) were used. We constructed models including more SNPs progressively lowering the threshold of inclusion (i.e. p<0.000001, p<0.00001, p<0.0001, p<0.001, p<0.01, p<0.1, p<0.5). Profiles derived from IOP SNP effects were tested for association with the phenotype (POAG here) using a logistic regression. Variance explained was assessed using Nagelkerke’s pseudoR<sup><xref rid="R2" ref-type="bibr">2</xref></sup> measure<sup><xref rid="R52" ref-type="bibr">52</xref></sup>.</p><p id="P31">To assess whether and to what degree IOP levels confer POAG risk, we performed a causal inference analysis using an instrumental variable framework as previously described<sup><xref rid="R15" ref-type="bibr">15</xref></sup>. In brief, we obtained estimates of effect size (Beta<sub>IOP</sub>) for the association of a given SNP with IOP from the meta-analysis of the 18 discovery cohorts. For the association of a given SNP with POAG, we obtained estimates of the effect size (Beta<sub>POAG</sub>) from the four case-control panels as described above. We selected the the strongest associated SNP from each of the genome-wide significant IOP loci that we identified. To assess whether the strength of SNPs’ association with IOP predicts the risk of POAG, we conducted linear regression analysis using the effect sizes of each SNP for IOP (Beta<sub>IOP</sub>) as independent variables and the effect sizes of POAG (Beta<sub>POAG</sub>) as dependent outcome variables . A total of eight independent IOP-associated SNPs were used for this analysis, including rs7555523 (<italic>TMCO1</italic>), rs6445055 (<italic>FNDC3B</italic>), rs10258482 (<italic>CAV1</italic>), rs2472493 (<italic>ABCA1</italic>), rs8176743 (<italic>ABO</italic>), rs747782 (<italic>NUP160-PTPRJ</italic>), and rs9913911 (<italic>GAS7</italic>).</p></sec><sec id="S6"><title>Gene expression in human tissues</title><p id="P32">Adult ocular samples were obtained from normal eyes of an 82-year-old European ancestry female from the North Carolina Eye Bank, Winston-Salem, North Carolina, USA. All adult ocular samples were stored in Qiagen’s RNA<italic>later</italic> within 6.5 hours of collection and shipped on dry ice overnight to the lab. Isolated tissues were snap-frozen and stored at −280 °C until RNA extraction. RNA was extracted from each tissue sample independently using the Ambion <italic>mir</italic>Vana total RNA extraction kit. The tissue samples were homogenized in Ambion lysis buffer using an Omni Bead Ruptor Tissue Homogenizer per protocol. Reverse transcription reactions were performed with Invitrogen SuperScript III First-Strand Synthesis kit. The expression of the identified genes were assessed by running 10 ul reactions with Qiagen’s PCR products consisting of 1.26 ul H2O, 1.0 ul 10X buffer, 1.0 ul dNTPs, 0.3 ul MgCl, 2.0 ul Q-Solution, 0.06 ul taq polymerase, 1.0 ul forward primer, 1.0 ul reverse primer and 1.5.0 ul cDNA. The reactions were run on a Eppendorf Mastercycler Pro S thermocycler with touchdown PCR ramping down 1°C per cycle from 72 °C to 55 °C followed by 50 cycles of 94 °C for 30 seconds, 55 °C for 30 seconds and 72 °C for 30 seconds with a final elongation of 7 minutes at 72 °C. All primer sets were designed using Primer3.<sup><xref rid="R53" ref-type="bibr">53</xref></sup> Products were run on a 2% agarose gel at 70 volts for 35 minutes. Primer sets were run on a custom tissue panel including Clontech’s Human MTC Panel I, Fetal MTC Panel I and an ocular tissue panel.</p></sec></sec><sec sec-type="supplementary-material" id="SM"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="SD1"><label>Supplementary Material</label><media xlink:href="NIHMS59965-supplement-1.pdf" orientation="portrait" xlink:type="simple" id="d37e1907" position="anchor"></media></supplementary-material></sec></body><back><ack id="S7"><title>ACKNOWLEDGMENTS</title><p>We gratefully acknowledge contributions of all participants who volunteered within each cohort, and the personnel responsible for the recruitment and administration of each study. We also thank the various funding sources that made this work possible. 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cohorts and checked for transcription regulation activity in three tissues from 856 British subjects.</p></caption><graphic xlink:href="emss-59965-f0001"></graphic></fig><fig id="F2" orientation="portrait" position="float"><label>Figure 2</label><caption><title>Manhattan plots of the results from the meta-analyses of results from 18 multi-ethnic cohorts from the IGGC</title><p>The 22 autosomes are plotted along the x-axis, whereas the values in the y-axis denote the −log10 -transformed p-values from the meta-analysis of association with IOP observed for any of the SNPs. Loci previously associated with IOP or glaucoma have been grayed out.</p></caption><graphic xlink:href="emss-59965-f0002"></graphic></fig><table-wrap id="T1" position="float" orientation="landscape"><label>Table 1</label><caption><title>Results for the association with Intraocular Pressure from the general population cohorts for SNPs significant at a multiple testing correction level (p<5×10<sup>−08</sup>) and their association with POAG in a case-control validation meta-analyses <xref ref-type="table-fn" rid="TFN1">*</xref></title></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="5" align="right" valign="middle" rowspan="1">SNP<hr></hr></th><th colspan="5" align="center" valign="middle" rowspan="1">Association with IOP in discovery cohort<hr></hr></th><th colspan="4" align="center" valign="middle" rowspan="1">Association in POAG Case-Controls<hr></hr></th></tr><tr><th align="right" valign="middle" rowspan="1" colspan="1">Chr.</th><th align="center" valign="middle" rowspan="1" colspan="1">Position</th><th align="center" valign="middle" rowspan="1" colspan="1">id</th><th align="center" valign="middle" rowspan="1" colspan="1">A1/A2</th><th align="center" valign="middle" rowspan="1" colspan="1">Nearest Gene</th><th align="center" valign="middle" rowspan="1" colspan="1">Beta</th><th align="center" valign="middle" rowspan="1" colspan="1">SE</th><th align="center" valign="middle" rowspan="1" colspan="1">p-value</th><th align="center" valign="middle" rowspan="1" colspan="1">Heterogeneity<break></break>p-value</th><th align="center" valign="middle" rowspan="1" colspan="1">I<sup>2</sup></th><th align="center" valign="middle" rowspan="1" colspan="1">OR</th><th colspan="2" align="center" valign="middle" rowspan="1">95% CIs</th><th align="center" valign="middle" rowspan="1" colspan="1">p value</th></tr></thead><tbody><tr><td align="right" valign="middle" rowspan="1" colspan="1">1</td><td align="center" valign="middle" rowspan="1" colspan="1">165687205</td><td align="center" valign="middle" rowspan="1" colspan="1">rs4656461</td><td align="center" valign="middle" rowspan="1" colspan="1">G/A</td><td align="center" valign="middle" rowspan="1" colspan="1">TMCO1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.228</td><td align="center" valign="middle" rowspan="1" colspan="1">0.039</td><td align="center" valign="middle" rowspan="1" colspan="1">6.51×10<sup>−09</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.46</td><td align="center" valign="middle" rowspan="1" colspan="1">0.00</td><td align="center" valign="middle" rowspan="1" colspan="1">1.38</td><td align="center" valign="middle" rowspan="1" colspan="1">1.28</td><td align="center" valign="middle" rowspan="1" colspan="1">1.5</td><td align="center" valign="middle" rowspan="1" colspan="1">2.55×10<sup>−15</sup></td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">1</td><td align="center" valign="middle" rowspan="1" colspan="1">165718979</td><td align="center" valign="middle" rowspan="1" colspan="1">rs7555523</td><td align="center" valign="middle" rowspan="1" colspan="1">C/A</td><td align="center" valign="middle" rowspan="1" colspan="1">TMCO1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.235</td><td align="center" valign="middle" rowspan="1" colspan="1">0.039</td><td align="center" valign="middle" rowspan="1" colspan="1">2.19×10<sup>−09</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.55</td><td align="center" valign="middle" rowspan="1" colspan="1">0.00</td><td align="center" valign="middle" rowspan="1" colspan="1">1.4</td><td align="center" valign="middle" rowspan="1" colspan="1">1.3</td><td align="center" valign="middle" rowspan="1" colspan="1">1.52</td><td align="center" valign="middle" rowspan="1" colspan="1">1.34×10<sup>−16</sup></td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">3</td><td align="center" valign="middle" rowspan="1" colspan="1">171992387</td><td align="center" valign="middle" rowspan="1" colspan="1">rs6445055</td><td align="center" valign="middle" rowspan="1" colspan="1">A/G</td><td align="center" valign="middle" rowspan="1" colspan="1">FNDC3B</td><td align="center" valign="middle" rowspan="1" colspan="1">−0.177</td><td align="center" valign="middle" rowspan="1" colspan="1">0.03</td><td align="center" valign="middle" rowspan="1" colspan="1">4.19×10<sup>−08</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.17</td><td align="center" valign="middle" rowspan="1" colspan="1">0.24</td><td align="center" valign="middle" rowspan="1" colspan="1">0.92</td><td align="center" valign="middle" rowspan="1" colspan="1">0.85</td><td align="center" valign="middle" rowspan="1" colspan="1">0.99</td><td align="center" valign="middle" rowspan="1" colspan="1">0.03</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">7</td><td align="center" valign="middle" rowspan="1" colspan="1">116150095</td><td align="center" valign="middle" rowspan="1" colspan="1">rs10258482</td><td align="center" valign="middle" rowspan="1" colspan="1">A/C</td><td align="center" valign="middle" rowspan="1" colspan="1">CAV1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.196</td><td align="center" valign="middle" rowspan="1" colspan="1">0.029</td><td align="center" valign="middle" rowspan="1" colspan="1">1.87×10<sup>−11</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.81</td><td align="center" valign="middle" rowspan="1" colspan="1">0.00</td><td align="center" valign="middle" rowspan="1" colspan="1">1.2</td><td align="center" valign="middle" rowspan="1" colspan="1">1.13</td><td align="center" valign="middle" rowspan="1" colspan="1">1.28</td><td align="center" valign="middle" rowspan="1" colspan="1">6.27×10<sup>−09</sup></td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">7</td><td align="center" valign="middle" rowspan="1" colspan="1">116150952</td><td align="center" valign="middle" rowspan="1" colspan="1">rs10262524</td><td align="center" valign="middle" rowspan="1" colspan="1">A/C</td><td align="center" valign="middle" rowspan="1" colspan="1">CAV1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.186</td><td align="center" valign="middle" rowspan="1" colspan="1">0.029</td><td align="center" valign="middle" rowspan="1" colspan="1">9.69×10<sup>−11</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.67</td><td align="center" valign="middle" rowspan="1" colspan="1">0.00</td><td align="center" valign="middle" rowspan="1" colspan="1">1.2</td><td align="center" valign="middle" rowspan="1" colspan="1">1.13</td><td align="center" valign="middle" rowspan="1" colspan="1">1.28</td><td align="center" valign="middle" rowspan="1" colspan="1">1.39×10<sup>−08</sup></td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">9</td><td align="center" valign="middle" rowspan="1" colspan="1">107695848</td><td align="center" valign="middle" rowspan="1" colspan="1">rs2472493</td><td align="center" valign="middle" rowspan="1" colspan="1">G/A</td><td align="center" valign="middle" rowspan="1" colspan="1">ABCA1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.159</td><td align="center" valign="middle" rowspan="1" colspan="1">0.024</td><td align="center" valign="middle" rowspan="1" colspan="1">2.80×10<sup>−11</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">4×10<sup>−05</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.66</td><td align="center" valign="middle" rowspan="1" colspan="1">1.24</td><td align="center" valign="middle" rowspan="1" colspan="1">1.16</td><td align="center" valign="middle" rowspan="1" colspan="1">1.34</td><td align="center" valign="middle" rowspan="1" colspan="1">4.15×10<sup>−09</sup></td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">9</td><td align="center" valign="middle" rowspan="1" colspan="1">136131415</td><td align="center" valign="middle" rowspan="1" colspan="1">rs8176743</td><td align="center" valign="middle" rowspan="1" colspan="1">T/C</td><td align="center" valign="middle" rowspan="1" colspan="1">ABO</td><td align="center" valign="middle" rowspan="1" colspan="1">0.261</td><td align="center" valign="middle" rowspan="1" colspan="1">0.039</td><td align="center" valign="middle" rowspan="1" colspan="1">3.08×10<sup>−11</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.53</td><td align="center" valign="middle" rowspan="1" colspan="1">0.00</td><td align="center" valign="middle" rowspan="1" colspan="1">1.07</td><td align="center" valign="middle" rowspan="1" colspan="1">0.96</td><td align="center" valign="middle" rowspan="1" colspan="1">1.19</td><td align="center" valign="middle" rowspan="1" colspan="1">0.2</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">11</td><td align="center" valign="middle" rowspan="1" colspan="1">47468545</td><td align="center" valign="middle" rowspan="1" colspan="1">rs12419342</td><td align="center" valign="middle" rowspan="1" colspan="1">C/T</td><td align="center" valign="middle" rowspan="1" colspan="1">RAPSN</td><td align="center" valign="middle" rowspan="1" colspan="1">0.153</td><td align="center" valign="middle" rowspan="1" colspan="1">0.026</td><td align="center" valign="middle" rowspan="1" colspan="1">4.77×10<sup>−09</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.75</td><td align="center" valign="middle" rowspan="1" colspan="1">0.00</td><td align="center" valign="middle" rowspan="1" colspan="1">1.09</td><td align="center" valign="middle" rowspan="1" colspan="1">1.02</td><td align="center" valign="middle" rowspan="1" colspan="1">1.16</td><td align="center" valign="middle" rowspan="1" colspan="1">0.008</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">11</td><td align="center" valign="middle" rowspan="1" colspan="1">47940925</td><td align="center" valign="middle" rowspan="1" colspan="1">rs747782</td><td align="center" valign="middle" rowspan="1" colspan="1">C/T</td><td align="center" valign="middle" rowspan="1" colspan="1">NUP160,PTPRJ</td><td align="center" valign="middle" rowspan="1" colspan="1">0.203</td><td align="center" valign="middle" rowspan="1" colspan="1">0.03</td><td align="center" valign="middle" rowspan="1" colspan="1">1.04×10<sup>−11</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.95</td><td align="center" valign="middle" rowspan="1" colspan="1">0.00</td><td align="center" valign="middle" rowspan="1" colspan="1">1.03</td><td align="center" valign="middle" rowspan="1" colspan="1">0.96</td><td align="center" valign="middle" rowspan="1" colspan="1">1.11</td><td align="center" valign="middle" rowspan="1" colspan="1">0.36</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">11</td><td align="center" valign="middle" rowspan="1" colspan="1">47969152</td><td align="center" valign="middle" rowspan="1" colspan="1">rs1681630</td><td align="center" valign="middle" rowspan="1" colspan="1">T/C</td><td align="center" valign="middle" rowspan="1" colspan="1">PTPRJ</td><td align="center" valign="middle" rowspan="1" colspan="1">0.144</td><td align="center" valign="middle" rowspan="1" colspan="1">0.026</td><td align="center" valign="middle" rowspan="1" colspan="1">1.69×10<sup>−08</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.6</td><td align="center" valign="middle" rowspan="1" colspan="1">0.00</td><td align="center" valign="middle" rowspan="1" colspan="1">1.06</td><td align="center" valign="middle" rowspan="1" colspan="1">0.99</td><td align="center" valign="middle" rowspan="1" colspan="1">1.12</td><td align="center" valign="middle" rowspan="1" colspan="1">0.08</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">11</td><td align="center" valign="middle" rowspan="1" colspan="1">48004369</td><td align="center" valign="middle" rowspan="1" colspan="1">rs7946766</td><td align="center" valign="middle" rowspan="1" colspan="1">T/C</td><td align="center" valign="middle" rowspan="1" colspan="1">PTPRJ</td><td align="center" valign="middle" rowspan="1" colspan="1">0.23</td><td align="center" valign="middle" rowspan="1" colspan="1">0.035</td><td align="center" valign="middle" rowspan="1" colspan="1">2.71×10<sup>−11</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.35</td><td align="center" valign="middle" rowspan="1" colspan="1">0.09</td><td align="center" valign="middle" rowspan="1" colspan="1">1.03</td><td align="center" valign="middle" rowspan="1" colspan="1">0.95</td><td align="center" valign="middle" rowspan="1" colspan="1">1.12</td><td align="center" valign="middle" rowspan="1" colspan="1">0.43</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">17</td><td align="center" valign="middle" rowspan="1" colspan="1">10031183</td><td align="center" valign="middle" rowspan="1" colspan="1">rs9913911</td><td align="center" valign="middle" rowspan="1" colspan="1">G/A</td><td align="center" valign="middle" rowspan="1" colspan="1">GAS7</td><td align="center" valign="middle" rowspan="1" colspan="1">−0.179</td><td align="center" valign="middle" rowspan="1" colspan="1">0.026</td><td align="center" valign="middle" rowspan="1" colspan="1">1.03×10<sup>−11</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">4×10<sup>−04</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.61</td><td align="center" valign="middle" rowspan="1" colspan="1">0.8</td><td align="center" valign="middle" rowspan="1" colspan="1">0.75</td><td align="center" valign="middle" rowspan="1" colspan="1">0.85</td><td align="center" valign="middle" rowspan="1" colspan="1">2.98×10<sup>−13</sup></td></tr></tbody></table><table-wrap-foot><fn id="TFN1"><label>*</label><p id="P33">Abbreviations used: Chr. - chromosome, A1/A2 - reference /alternative alleles, beta- linear regression coefficient (mmHg), SE-standard error of the regression coefficient, OR- Odds Ratios, 95% CIs – 95% Confidence interval for OR.</p></fn></table-wrap-foot></table-wrap><table-wrap id="T2" position="float" orientation="landscape"><label>Table 2</label><caption><title>Summary of eQTL effects observed in three different tissues extracted from 849 individuals for SNPs associated with IOP<xref ref-type="table-fn" rid="TFN2">*</xref></title><p>The SNPs listed are the same as those in <xref ref-type="table" rid="T1">Table 1</xref>.</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="5" align="right" valign="middle" rowspan="1">SNP<hr></hr></th><th colspan="5" align="center" valign="middle" rowspan="1">eQTL Effects p-values<hr></hr></th></tr><tr><th align="right" valign="middle" rowspan="1" colspan="1">Chr</th><th align="center" valign="middle" rowspan="1" colspan="1">Position</th><th align="center" valign="middle" rowspan="1" colspan="1">id</th><th align="center" valign="middle" rowspan="1" colspan="1">A1/A2</th><th align="center" valign="middle" rowspan="1" colspan="1">Nearest Gene</th><th align="center" valign="middle" rowspan="1" colspan="1">Adipose</th><th align="center" valign="middle" rowspan="1" colspan="1">LCL</th><th align="center" valign="middle" rowspan="1" colspan="1">Skin</th><th align="center" valign="middle" rowspan="1" colspan="1">Probe ID</th><th align="center" valign="middle" rowspan="1" colspan="1">Gene</th></tr></thead><tbody><tr><td align="right" valign="middle" rowspan="1" colspan="1">1</td><td align="center" valign="middle" rowspan="1" colspan="1">165687205</td><td align="center" valign="middle" rowspan="1" colspan="1">rs4656461</td><td align="center" valign="middle" rowspan="1" colspan="1">G/A</td><td align="center" valign="middle" rowspan="1" colspan="1">TMCO1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.004</td><td align="center" valign="middle" rowspan="1" colspan="1">0.12</td><td align="center" valign="middle" rowspan="1" colspan="1">0.003</td><td align="center" valign="middle" rowspan="1" colspan="1">ILMN_1793829</td><td align="center" valign="middle" rowspan="1" colspan="1">TMCO1</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">1</td><td align="center" valign="middle" rowspan="1" colspan="1">165718979</td><td align="center" valign="middle" rowspan="1" colspan="1">rs7555523</td><td align="center" valign="middle" rowspan="1" colspan="1">C/A</td><td align="center" valign="middle" rowspan="1" colspan="1">TMCO1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.39</td><td align="center" valign="middle" rowspan="1" colspan="1">0.0001</td><td align="center" valign="middle" rowspan="1" colspan="1">0.05</td><td align="center" valign="middle" rowspan="1" colspan="1">ILMN_1761804</td><td align="center" valign="middle" rowspan="1" colspan="1">ALDH9A1</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">3</td><td align="center" valign="middle" rowspan="1" colspan="1">171992387</td><td align="center" valign="middle" rowspan="1" colspan="1">rs6445055</td><td align="center" valign="middle" rowspan="1" colspan="1">A/G</td><td align="center" valign="middle" rowspan="1" colspan="1">FNDC3B</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">-</td><td align="center" valign="middle" rowspan="1" colspan="1">-</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">7</td><td align="center" valign="middle" rowspan="1" colspan="1">116150095</td><td align="center" valign="middle" rowspan="1" colspan="1">rs10258482</td><td align="center" valign="middle" rowspan="1" colspan="1">A/C</td><td align="center" valign="middle" rowspan="1" colspan="1">CAV1</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">-</td><td align="center" valign="middle" rowspan="1" colspan="1">-</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">7</td><td align="center" valign="middle" rowspan="1" colspan="1">116150952</td><td align="center" valign="middle" rowspan="1" colspan="1">rs10262524</td><td align="center" valign="middle" rowspan="1" colspan="1">A/C</td><td align="center" valign="middle" rowspan="1" colspan="1">CAV1</td><td align="center" valign="middle" rowspan="1" colspan="1">5.79×10<sup>−16</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">8.54×10<sup>−05</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">3.91×10<sup>−13</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">ILMN_1687583</td><td align="center" valign="middle" rowspan="1" colspan="1">CAV1</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">9</td><td align="center" valign="middle" rowspan="1" colspan="1">107695848</td><td align="center" valign="middle" rowspan="1" colspan="1">rs2472493</td><td align="center" valign="middle" rowspan="1" colspan="1">G/A</td><td align="center" valign="middle" rowspan="1" colspan="1">ABCA1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.19</td><td align="center" valign="middle" rowspan="1" colspan="1">3.67×10<sup>−05</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.36</td><td align="center" valign="middle" rowspan="1" colspan="1">ILMN_1766054</td><td align="center" valign="middle" rowspan="1" colspan="1">ABCA1</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">9</td><td align="center" valign="middle" rowspan="1" colspan="1">136131415</td><td align="center" valign="middle" rowspan="1" colspan="1">rs8176743</td><td align="center" valign="middle" rowspan="1" colspan="1">T/C</td><td align="center" valign="middle" rowspan="1" colspan="1">ABO</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">-</td><td align="center" valign="middle" rowspan="1" colspan="1">-</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">11</td><td align="center" valign="middle" rowspan="1" colspan="1">47468545</td><td align="center" valign="middle" rowspan="1" colspan="1">rs12419342</td><td align="center" valign="middle" rowspan="1" colspan="1">C/T</td><td align="center" valign="middle" rowspan="1" colspan="1">RAPSN</td><td align="center" valign="middle" rowspan="1" colspan="1">0.002</td><td align="center" valign="middle" rowspan="1" colspan="1">4.32×10<sup>−08</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.0003</td><td align="center" valign="middle" rowspan="1" colspan="1">ILMN_1696463</td><td align="center" valign="middle" rowspan="1" colspan="1">SPI1</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">11</td><td align="center" valign="middle" rowspan="1" colspan="1">47940925</td><td align="center" valign="middle" rowspan="1" colspan="1">rs747782</td><td align="center" valign="middle" rowspan="1" colspan="1">C/T</td><td align="center" valign="middle" rowspan="1" colspan="1">NUP160,PTPRJ</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">-</td><td align="center" valign="middle" rowspan="1" colspan="1">-</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">11</td><td align="center" valign="middle" rowspan="1" colspan="1">47969152</td><td align="center" valign="middle" rowspan="1" colspan="1">rs1681630</td><td align="center" valign="middle" rowspan="1" colspan="1">T/C</td><td align="center" valign="middle" rowspan="1" colspan="1">PTPRJ</td><td align="center" valign="middle" rowspan="1" colspan="1">0.006</td><td align="center" valign="middle" rowspan="1" colspan="1">2.72×10<sup>−10</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.002</td><td align="center" valign="middle" rowspan="1" colspan="1">ILMN_1696463</td><td align="center" valign="middle" rowspan="1" colspan="1">SPI1</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">11</td><td align="center" valign="middle" rowspan="1" colspan="1">48004369</td><td align="center" valign="middle" rowspan="1" colspan="1">rs7946766</td><td align="center" valign="middle" rowspan="1" colspan="1">T/C</td><td align="center" valign="middle" rowspan="1" colspan="1">PTPRJ</td><td align="center" valign="middle" rowspan="1" colspan="1">0.66</td><td align="center" valign="middle" rowspan="1" colspan="1">2.02×10<sup>−05</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">0.0066</td><td align="center" valign="middle" rowspan="1" colspan="1">ILMN_1688627</td><td align="center" valign="middle" rowspan="1" colspan="1">AGBL2</td></tr><tr><td align="right" valign="middle" rowspan="1" colspan="1">17</td><td align="center" valign="middle" rowspan="1" colspan="1">10031183</td><td align="center" valign="middle" rowspan="1" colspan="1">rs9913911</td><td align="center" valign="middle" rowspan="1" colspan="1">G/A</td><td align="center" valign="middle" rowspan="1" colspan="1">GAS7</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">N.S.</td><td align="center" valign="middle" rowspan="1" colspan="1">-</td><td align="center" valign="middle" rowspan="1" colspan="1">-</td></tr></tbody></table><table-wrap-foot><fn id="TFN2"><label>*</label><p id="P34">Abbreviations used: LCL- lymphoblastoid cell lines, N.S. – no significant association detected</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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