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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium</title><author><name sortKey="Verhoeven, Virginie J M" sort="Verhoeven, Virginie J M" uniqKey="Verhoeven V" first="Virginie J. M." last="Verhoeven">Virginie J. M. Verhoeven</name><affiliation><nlm:aff id="Aff1">Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation></author><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="Aff3">Department of Twin Research and Genetic Epidemiology, King’s College London, St. Thomas’ Hospital, London, UK</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="Aff4">Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff5">Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore</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="Aff6">Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, 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="Aff7">Department of Ophthalmology, J. Gutenberg University Medical Center, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="Guggenheim, Jeremy A" sort="Guggenheim, Jeremy A" uniqKey="Guggenheim J" first="Jeremy A." last="Guggenheim">Jeremy A. Guggenheim</name><affiliation><nlm:aff id="Aff8">School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK</nlm:aff></affiliation></author><author><name sortKey="Cotch, Mary Frances" sort="Cotch, Mary Frances" uniqKey="Cotch M" first="Mary Frances" last="Cotch">Mary Frances Cotch</name><affiliation><nlm:aff id="Aff9">Division of Epidemiology and Clinical Applications, National Eye Institute, Intramural Research Program, National Institutes of Health, Bethesda, USA</nlm:aff></affiliation></author><author><name sortKey="Yamashiro, Kenji" sort="Yamashiro, Kenji" uniqKey="Yamashiro K" first="Kenji" last="Yamashiro">Kenji Yamashiro</name><affiliation><nlm:aff id="Aff10">Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan</nlm:aff></affiliation></author><author><name sortKey="Baird, Paul N" sort="Baird, Paul N" uniqKey="Baird P" first="Paul N." last="Baird">Paul N. Baird</name><affiliation><nlm:aff id="Aff11">Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia</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="Aff11">Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="Aff12">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia</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="Aff13">Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff14">Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, USA</nlm:aff></affiliation></author><author><name sortKey=" Ikram, M Kamran" sort=" Ikram, M Kamran" uniqKey=" Ikram M" first="M. Kamran" last=" Ikram">M. Kamran Ikram</name><affiliation><nlm:aff id="Aff1">Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff15">Department of Ophthalmology, National University Health System, National University of Singapore, Singapore, Singapore</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="Aff11">Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Duggal, Priya" sort="Duggal, Priya" uniqKey="Duggal P" first="Priya" last="Duggal">Priya Duggal</name><affiliation><nlm:aff id="Aff13">Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA</nlm:aff></affiliation></author><author><name sortKey="Janmahasatian, Sarayut" sort="Janmahasatian, Sarayut" uniqKey="Janmahasatian S" first="Sarayut" last="Janmahasatian">Sarayut Janmahasatian</name><affiliation><nlm:aff id="Aff16">Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, USA</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="Aff17">Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Fan, Qiao" sort="Fan, Qiao" uniqKey="Fan Q" first="Qiao" last="Fan">Qiao Fan</name><affiliation><nlm:aff id="Aff4">Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Zhou, Xin" sort="Zhou, Xin" uniqKey="Zhou X" first="Xin" last="Zhou">Xin Zhou</name><affiliation><nlm:aff id="Aff4">Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</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="Aff18">Center for Human Genetics, Duke University Medical Center, Durham, USA</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="Aff19">Department of Medicine, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Goh, Liang Kee" sort="Goh, Liang Kee" uniqKey="Goh L" first="Liang-Kee" last="Goh">Liang-Kee Goh</name><affiliation><nlm:aff id="Aff4">Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff20">Duke-National University of Singapore Graduate Medical School, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi-Ju" last="Li">Yi-Ju Li</name><affiliation><nlm:aff id="Aff18">Center for Human Genetics, Duke University Medical Center, Durham, USA</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="Aff5">Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff15">Department of Ophthalmology, National University Health System, National University of Singapore, Singapore, Singapore</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="Aff5">Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff15">Department of Ophthalmology, National University Health System, National University of Singapore, Singapore, Singapore</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="Aff4">Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff21">Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff22">Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Tay, Wanting" sort="Tay, Wanting" uniqKey="Tay W" first="Wanting" last="Tay">Wanting Tay</name><affiliation><nlm:aff id="Aff5">Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Sim, Xueling" sort="Sim, Xueling" uniqKey="Sim X" first="Xueling" last="Sim">Xueling Sim</name><affiliation><nlm:aff id="Aff22">Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Rudan, Igor" sort="Rudan, Igor" uniqKey="Rudan I" first="Igor" last="Rudan">Igor Rudan</name><affiliation><nlm:aff id="Aff23">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Hayward, Caroline" sort="Hayward, Caroline" uniqKey="Hayward C" first="Caroline" last="Hayward">Caroline Hayward</name><affiliation><nlm:aff id="Aff6">Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Wright, Alan F" sort="Wright, Alan F" uniqKey="Wright A" first="Alan F." last="Wright">Alan F. Wright</name><affiliation><nlm:aff id="Aff6">Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Polasek, Ozren" sort="Polasek, Ozren" uniqKey="Polasek O" first="Ozren" last="Polasek">Ozren Polasek</name><affiliation><nlm:aff id="Aff24">Faculty of Medicine, University of Split, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Campbell, Harry" sort="Campbell, Harry" uniqKey="Campbell H" first="Harry" last="Campbell">Harry Campbell</name><affiliation><nlm:aff id="Aff23">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</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="Aff23">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</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="Aff25">Princess Alexandra Eye Pavilion, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Nakata, Isao" sort="Nakata, Isao" uniqKey="Nakata I" first="Isao" last="Nakata">Isao Nakata</name><affiliation><nlm:aff id="Aff10">Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan</nlm:aff></affiliation></author><author><name sortKey="Yoshimura, Nagahisa" sort="Yoshimura, Nagahisa" uniqKey="Yoshimura N" first="Nagahisa" last="Yoshimura">Nagahisa Yoshimura</name><affiliation><nlm:aff id="Aff10">Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan</nlm:aff></affiliation></author><author><name sortKey="Yamada, Ryo" sort="Yamada, Ryo" uniqKey="Yamada R" first="Ryo" last="Yamada">Ryo Yamada</name><affiliation><nlm:aff id="Aff26">Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan</nlm:aff></affiliation></author><author><name sortKey="Matsuda, Fumihiko" sort="Matsuda, Fumihiko" uniqKey="Matsuda F" first="Fumihiko" last="Matsuda">Fumihiko Matsuda</name><affiliation><nlm:aff id="Aff26">Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan</nlm:aff></affiliation></author><author><name sortKey="Ohno Matsui, Kyoko" sort="Ohno Matsui, Kyoko" uniqKey="Ohno Matsui K" first="Kyoko" last="Ohno-Matsui">Kyoko Ohno-Matsui</name><affiliation><nlm:aff id="Aff27">Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan</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="Aff3">Department of Twin Research and Genetic Epidemiology, King’s College London, St. Thomas’ Hospital, London, UK</nlm:aff></affiliation></author><author><name sortKey="Mcmahon, George" sort="Mcmahon, George" uniqKey="Mcmahon G" first="George" last="Mcmahon">George Mcmahon</name><affiliation><nlm:aff id="Aff28">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Pourcain, Beate St" sort="Pourcain, Beate St" uniqKey="Pourcain B" first="Beate St." last="Pourcain">Beate St. Pourcain</name><affiliation><nlm:aff id="Aff28">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Lu, Yi" sort="Lu, Yi" uniqKey="Lu Y" first="Yi" last="Lu">Yi Lu</name><affiliation><nlm:aff id="Aff29">Department of Genetics and Population Health, Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Rahi, Jugnoo S" sort="Rahi, Jugnoo S" uniqKey="Rahi J" first="Jugnoo S." last="Rahi">Jugnoo S. Rahi</name><affiliation><nlm:aff id="Aff30">Medical Research Council Centre of Epidemiology for Child Health, Institute of Child Health, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="Aff31">Institute of Ophthalmology, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Cumberland, Phillippa M" sort="Cumberland, Phillippa M" uniqKey="Cumberland P" first="Phillippa M." last="Cumberland">Phillippa M. Cumberland</name><affiliation><nlm:aff id="Aff30">Medical Research Council Centre of Epidemiology for Child Health, Institute of Child Health, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="Aff32">Ulverscroft Vision Research Group, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Bhattacharya, Shomi" sort="Bhattacharya, Shomi" uniqKey="Bhattacharya S" first="Shomi" last="Bhattacharya">Shomi Bhattacharya</name><affiliation><nlm:aff id="Aff31">Institute of Ophthalmology, University College London, London, UK</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="Aff14">Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, USA</nlm:aff></affiliation></author><author><name sortKey="Atwood, Larry D" sort="Atwood, Larry D" uniqKey="Atwood L" first="Larry D." last="Atwood">Larry D. Atwood</name><affiliation><nlm:aff id="Aff33">Department of Neurology, Boston University School of Medicine, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Li, Xiaohui" sort="Li, Xiaohui" uniqKey="Li X" first="Xiaohui" last="Li">Xiaohui Li</name><affiliation><nlm:aff id="Aff34">Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, USA</nlm:aff></affiliation></author><author><name sortKey="Raffel, Leslie J" sort="Raffel, Leslie J" uniqKey="Raffel L" first="Leslie J." last="Raffel">Leslie J. Raffel</name><affiliation><nlm:aff id="Aff34">Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, USA</nlm:aff></affiliation></author><author><name sortKey="Murgia, Federico" sort="Murgia, Federico" uniqKey="Murgia F" first="Federico" last="Murgia">Federico Murgia</name><affiliation><nlm:aff id="Aff35">Institute of Population Genetics, National Research Council, Sassari, Italy</nlm:aff></affiliation></author><author><name sortKey="Portas, Laura" sort="Portas, Laura" uniqKey="Portas L" first="Laura" last="Portas">Laura Portas</name><affiliation><nlm:aff id="Aff35">Institute of Population Genetics, National Research Council, Sassari, Italy</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="Aff1">Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff36">Glaucoma Service, The Rotterdam Eye Hospital, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wolfram, Christian" sort="Wolfram, Christian" uniqKey="Wolfram C" first="Christian" last="Wolfram">Christian Wolfram</name><affiliation><nlm:aff id="Aff7">Department of Ophthalmology, J. Gutenberg University Medical Center, Mainz, Germany</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="Aff7">Department of Ophthalmology, J. Gutenberg University Medical Center, Mainz, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="Aff37">Institute of Clinical Chemistry and Laboratory Medicine, J. Gutenberg University Medical Center, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="Tonjes, Anke" sort="Tonjes, Anke" uniqKey="Tonjes A" first="Anke" last="Tönjes">Anke Tönjes</name><affiliation><nlm:aff id="Aff38">Department of Medicine, University of Leipzig, Leipzig, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="Aff39">Integrated Research and Treatment Center (IFB) AdiposityDiseases, University of Leipzig, Leipzig, Germany</nlm:aff></affiliation></author><author><name sortKey="M Gi, Reedik" sort="M Gi, Reedik" uniqKey="M Gi R" first="Reedik" last="M Gi">Reedik M Gi</name><affiliation><nlm:aff id="Aff40">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="Aff41">The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Lehtim Ki, Terho" sort="Lehtim Ki, Terho" uniqKey="Lehtim Ki T" first="Terho" last="Lehtim Ki">Terho Lehtim Ki</name><affiliation><nlm:aff id="Aff42">Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="Aff43">University of Tampere School of Medicine, Tampere, Finland</nlm:aff></affiliation></author><author><name sortKey="K Honen, Mika" sort="K Honen, Mika" uniqKey="K Honen M" first="Mika" last="K Hönen">Mika K Hönen</name><affiliation><nlm:aff id="Aff44">Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="Aff45">Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland</nlm:aff></affiliation></author><author><name sortKey="Esko, T Nu" sort="Esko, T Nu" uniqKey="Esko T" first="T Nu" last="Esko">T Nu Esko</name><affiliation><nlm:aff id="Aff40">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Metspalu, Andres" sort="Metspalu, Andres" uniqKey="Metspalu A" first="Andres" last="Metspalu">Andres Metspalu</name><affiliation><nlm:aff id="Aff40">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Rantanen, Taina" sort="Rantanen, Taina" uniqKey="Rantanen T" first="Taina" last="Rantanen">Taina Rantanen</name><affiliation><nlm:aff id="Aff46">Department of Health Sciences, Gerontology Research Center, University of Jyväskylä, Jyväskylä, Finland</nlm:aff></affiliation></author><author><name sortKey="P Rssinen, Olavi" sort="P Rssinen, Olavi" uniqKey="P Rssinen O" first="Olavi" last="P Rssinen">Olavi P Rssinen</name><affiliation><nlm:aff id="Aff47">Department of Ophthalmology, Central Hospital of Central Finland, Jyväskylä, Finland</nlm:aff></affiliation></author><author><name sortKey="Klein, Barbara E" sort="Klein, Barbara E" uniqKey="Klein B" first="Barbara E." last="Klein">Barbara E. Klein</name><affiliation><nlm:aff id="Aff48">Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, USA</nlm:aff></affiliation></author><author><name sortKey="Meitinger, Thomas" sort="Meitinger, Thomas" uniqKey="Meitinger T" first="Thomas" last="Meitinger">Thomas Meitinger</name><affiliation><nlm:aff id="Aff49">Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="Aff50">Institute of Human Genetics, Technical University Munich, Munich, Germany</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="Aff3">Department of Twin Research and Genetic Epidemiology, King’s College London, St. Thomas’ Hospital, London, UK</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="Aff51">Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Smith, Albert V" sort="Smith, Albert V" uniqKey="Smith A" first="Albert V." last="Smith">Albert V. Smith</name><affiliation><nlm:aff id="Aff52">Department of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="Aff53">Icelandic Heart Association, Kopavogur, Iceland</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="Aff63">Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff54">Department of Clinical and Molecular Ophthalmogenetics, Netherlands Institute of Neurosciences (NIN), An Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff55">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 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="Aff1">Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Eiriksd Ttir, Gu N" sort="Eiriksd Ttir, Gu N" uniqKey="Eiriksd Ttir G" first="Gu N" last="Eiríksd Ttir">Gu N Eiríksd Ttir</name><affiliation><nlm:aff id="Aff53">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name><affiliation><nlm:aff id="Aff52">Department of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="Aff53">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Doring, Angela" sort="Doring, Angela" uniqKey="Doring A" first="Angela" last="Döring">Angela Döring</name><affiliation><nlm:aff id="Aff64">Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Bettecken, Thomas" sort="Bettecken, Thomas" uniqKey="Bettecken T" first="Thomas" last="Bettecken">Thomas Bettecken</name><affiliation><nlm:aff id="Aff56">Center for Applied Genotyping, Max Planck Institute of Psychiatry, German Research Institute of Psychiatry, Munich, Germany</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff55">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Williams, Cathy" sort="Williams, Cathy" uniqKey="Williams C" first="Cathy" last="Williams">Cathy Williams</name><affiliation><nlm:aff id="Aff57">Centre for Child and Adolescent Health, University of Bristol, Bristol, 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="Aff58">Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Castagne, Raphaele" sort="Castagne, Raphaele" uniqKey="Castagne R" first="Raphaële" last="Castagné">Raphaële Castagné</name><affiliation><nlm:aff id="Aff59">INSERM UMRS 937, Pierre and Marie Curie University (UPMC, Paris 6) and Medical School, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Oexle, Konrad" sort="Oexle, Konrad" uniqKey="Oexle K" first="Konrad" last="Oexle">Konrad Oexle</name><affiliation><nlm:aff id="Aff50">Institute of Human Genetics, Technical University Munich, Munich, Germany</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Iyengar, Sudha K" sort="Iyengar, Sudha K" uniqKey="Iyengar S" first="Sudha K." last="Iyengar">Sudha K. Iyengar</name><affiliation><nlm:aff id="Aff16">Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, USA</nlm:aff></affiliation></author><author><name sortKey="Mitchell, Paul" sort="Mitchell, Paul" uniqKey="Mitchell P" first="Paul" last="Mitchell">Paul Mitchell</name><affiliation><nlm:aff id="Aff60">Department of Ophthalmology, Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Wang, Jie Jin" sort="Wang, Jie Jin" uniqKey="Wang J" first="Jie Jin" last="Wang">Jie Jin Wang</name><affiliation><nlm:aff id="Aff11">Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="Aff60">Department of Ophthalmology, Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Sydney, 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="Aff7">Department of Ophthalmology, J. Gutenberg University Medical Center, Mainz, Germany</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="Aff7">Department of Ophthalmology, J. Gutenberg University Medical Center, Mainz, Germany</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="Aff14">Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, USA</nlm:aff></affiliation></author><author><name sortKey="Stambolian, Dwight" sort="Stambolian, Dwight" uniqKey="Stambolian D" first="Dwight" last="Stambolian">Dwight Stambolian</name><affiliation><nlm:aff id="Aff61">Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA</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="Aff4">Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff5">Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff15">Department of Ophthalmology, National University Health System, National University of Singapore, Singapore, Singapore</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="Aff3">Department of Twin Research and Genetic Epidemiology, King’s College London, St. Thomas’ Hospital, 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="Aff1">Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22665138</idno><idno type="pmc">3418496</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418496</idno><idno type="RBID">PMC:3418496</idno><idno type="doi">10.1007/s00439-012-1176-0</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000D31</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000D31</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium</title><author><name sortKey="Verhoeven, Virginie J M" sort="Verhoeven, Virginie J M" uniqKey="Verhoeven V" first="Virginie J. M." last="Verhoeven">Virginie J. M. Verhoeven</name><affiliation><nlm:aff id="Aff1">Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation></author><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="Aff3">Department of Twin Research and Genetic Epidemiology, King’s College London, St. Thomas’ Hospital, London, UK</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="Aff4">Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff5">Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore</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="Aff6">Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, 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="Aff7">Department of Ophthalmology, J. Gutenberg University Medical Center, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="Guggenheim, Jeremy A" sort="Guggenheim, Jeremy A" uniqKey="Guggenheim J" first="Jeremy A." last="Guggenheim">Jeremy A. Guggenheim</name><affiliation><nlm:aff id="Aff8">School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK</nlm:aff></affiliation></author><author><name sortKey="Cotch, Mary Frances" sort="Cotch, Mary Frances" uniqKey="Cotch M" first="Mary Frances" last="Cotch">Mary Frances Cotch</name><affiliation><nlm:aff id="Aff9">Division of Epidemiology and Clinical Applications, National Eye Institute, Intramural Research Program, National Institutes of Health, Bethesda, USA</nlm:aff></affiliation></author><author><name sortKey="Yamashiro, Kenji" sort="Yamashiro, Kenji" uniqKey="Yamashiro K" first="Kenji" last="Yamashiro">Kenji Yamashiro</name><affiliation><nlm:aff id="Aff10">Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan</nlm:aff></affiliation></author><author><name sortKey="Baird, Paul N" sort="Baird, Paul N" uniqKey="Baird P" first="Paul N." last="Baird">Paul N. Baird</name><affiliation><nlm:aff id="Aff11">Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia</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="Aff11">Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="Aff12">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia</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="Aff13">Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff14">Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, USA</nlm:aff></affiliation></author><author><name sortKey=" Ikram, M Kamran" sort=" Ikram, M Kamran" uniqKey=" Ikram M" first="M. Kamran" last=" Ikram">M. Kamran Ikram</name><affiliation><nlm:aff id="Aff1">Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff15">Department of Ophthalmology, National University Health System, National University of Singapore, Singapore, Singapore</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="Aff11">Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Duggal, Priya" sort="Duggal, Priya" uniqKey="Duggal P" first="Priya" last="Duggal">Priya Duggal</name><affiliation><nlm:aff id="Aff13">Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA</nlm:aff></affiliation></author><author><name sortKey="Janmahasatian, Sarayut" sort="Janmahasatian, Sarayut" uniqKey="Janmahasatian S" first="Sarayut" last="Janmahasatian">Sarayut Janmahasatian</name><affiliation><nlm:aff id="Aff16">Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, USA</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="Aff17">Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Fan, Qiao" sort="Fan, Qiao" uniqKey="Fan Q" first="Qiao" last="Fan">Qiao Fan</name><affiliation><nlm:aff id="Aff4">Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Zhou, Xin" sort="Zhou, Xin" uniqKey="Zhou X" first="Xin" last="Zhou">Xin Zhou</name><affiliation><nlm:aff id="Aff4">Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</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="Aff18">Center for Human Genetics, Duke University Medical Center, Durham, USA</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="Aff19">Department of Medicine, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Goh, Liang Kee" sort="Goh, Liang Kee" uniqKey="Goh L" first="Liang-Kee" last="Goh">Liang-Kee Goh</name><affiliation><nlm:aff id="Aff4">Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff20">Duke-National University of Singapore Graduate Medical School, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi-Ju" last="Li">Yi-Ju Li</name><affiliation><nlm:aff id="Aff18">Center for Human Genetics, Duke University Medical Center, Durham, USA</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="Aff5">Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff15">Department of Ophthalmology, National University Health System, National University of Singapore, Singapore, Singapore</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="Aff5">Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff15">Department of Ophthalmology, National University Health System, National University of Singapore, Singapore, Singapore</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="Aff4">Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff21">Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff22">Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Tay, Wanting" sort="Tay, Wanting" uniqKey="Tay W" first="Wanting" last="Tay">Wanting Tay</name><affiliation><nlm:aff id="Aff5">Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Sim, Xueling" sort="Sim, Xueling" uniqKey="Sim X" first="Xueling" last="Sim">Xueling Sim</name><affiliation><nlm:aff id="Aff22">Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Rudan, Igor" sort="Rudan, Igor" uniqKey="Rudan I" first="Igor" last="Rudan">Igor Rudan</name><affiliation><nlm:aff id="Aff23">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Hayward, Caroline" sort="Hayward, Caroline" uniqKey="Hayward C" first="Caroline" last="Hayward">Caroline Hayward</name><affiliation><nlm:aff id="Aff6">Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Wright, Alan F" sort="Wright, Alan F" uniqKey="Wright A" first="Alan F." last="Wright">Alan F. Wright</name><affiliation><nlm:aff id="Aff6">Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Polasek, Ozren" sort="Polasek, Ozren" uniqKey="Polasek O" first="Ozren" last="Polasek">Ozren Polasek</name><affiliation><nlm:aff id="Aff24">Faculty of Medicine, University of Split, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Campbell, Harry" sort="Campbell, Harry" uniqKey="Campbell H" first="Harry" last="Campbell">Harry Campbell</name><affiliation><nlm:aff id="Aff23">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</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="Aff23">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</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="Aff25">Princess Alexandra Eye Pavilion, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Nakata, Isao" sort="Nakata, Isao" uniqKey="Nakata I" first="Isao" last="Nakata">Isao Nakata</name><affiliation><nlm:aff id="Aff10">Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan</nlm:aff></affiliation></author><author><name sortKey="Yoshimura, Nagahisa" sort="Yoshimura, Nagahisa" uniqKey="Yoshimura N" first="Nagahisa" last="Yoshimura">Nagahisa Yoshimura</name><affiliation><nlm:aff id="Aff10">Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan</nlm:aff></affiliation></author><author><name sortKey="Yamada, Ryo" sort="Yamada, Ryo" uniqKey="Yamada R" first="Ryo" last="Yamada">Ryo Yamada</name><affiliation><nlm:aff id="Aff26">Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan</nlm:aff></affiliation></author><author><name sortKey="Matsuda, Fumihiko" sort="Matsuda, Fumihiko" uniqKey="Matsuda F" first="Fumihiko" last="Matsuda">Fumihiko Matsuda</name><affiliation><nlm:aff id="Aff26">Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan</nlm:aff></affiliation></author><author><name sortKey="Ohno Matsui, Kyoko" sort="Ohno Matsui, Kyoko" uniqKey="Ohno Matsui K" first="Kyoko" last="Ohno-Matsui">Kyoko Ohno-Matsui</name><affiliation><nlm:aff id="Aff27">Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan</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="Aff3">Department of Twin Research and Genetic Epidemiology, King’s College London, St. Thomas’ Hospital, London, UK</nlm:aff></affiliation></author><author><name sortKey="Mcmahon, George" sort="Mcmahon, George" uniqKey="Mcmahon G" first="George" last="Mcmahon">George Mcmahon</name><affiliation><nlm:aff id="Aff28">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Pourcain, Beate St" sort="Pourcain, Beate St" uniqKey="Pourcain B" first="Beate St." last="Pourcain">Beate St. Pourcain</name><affiliation><nlm:aff id="Aff28">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Lu, Yi" sort="Lu, Yi" uniqKey="Lu Y" first="Yi" last="Lu">Yi Lu</name><affiliation><nlm:aff id="Aff29">Department of Genetics and Population Health, Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Rahi, Jugnoo S" sort="Rahi, Jugnoo S" uniqKey="Rahi J" first="Jugnoo S." last="Rahi">Jugnoo S. Rahi</name><affiliation><nlm:aff id="Aff30">Medical Research Council Centre of Epidemiology for Child Health, Institute of Child Health, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="Aff31">Institute of Ophthalmology, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Cumberland, Phillippa M" sort="Cumberland, Phillippa M" uniqKey="Cumberland P" first="Phillippa M." last="Cumberland">Phillippa M. Cumberland</name><affiliation><nlm:aff id="Aff30">Medical Research Council Centre of Epidemiology for Child Health, Institute of Child Health, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="Aff32">Ulverscroft Vision Research Group, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Bhattacharya, Shomi" sort="Bhattacharya, Shomi" uniqKey="Bhattacharya S" first="Shomi" last="Bhattacharya">Shomi Bhattacharya</name><affiliation><nlm:aff id="Aff31">Institute of Ophthalmology, University College London, London, UK</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="Aff14">Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, USA</nlm:aff></affiliation></author><author><name sortKey="Atwood, Larry D" sort="Atwood, Larry D" uniqKey="Atwood L" first="Larry D." last="Atwood">Larry D. Atwood</name><affiliation><nlm:aff id="Aff33">Department of Neurology, Boston University School of Medicine, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Li, Xiaohui" sort="Li, Xiaohui" uniqKey="Li X" first="Xiaohui" last="Li">Xiaohui Li</name><affiliation><nlm:aff id="Aff34">Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, USA</nlm:aff></affiliation></author><author><name sortKey="Raffel, Leslie J" sort="Raffel, Leslie J" uniqKey="Raffel L" first="Leslie J." last="Raffel">Leslie J. Raffel</name><affiliation><nlm:aff id="Aff34">Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, USA</nlm:aff></affiliation></author><author><name sortKey="Murgia, Federico" sort="Murgia, Federico" uniqKey="Murgia F" first="Federico" last="Murgia">Federico Murgia</name><affiliation><nlm:aff id="Aff35">Institute of Population Genetics, National Research Council, Sassari, Italy</nlm:aff></affiliation></author><author><name sortKey="Portas, Laura" sort="Portas, Laura" uniqKey="Portas L" first="Laura" last="Portas">Laura Portas</name><affiliation><nlm:aff id="Aff35">Institute of Population Genetics, National Research Council, Sassari, Italy</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="Aff1">Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff36">Glaucoma Service, The Rotterdam Eye Hospital, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wolfram, Christian" sort="Wolfram, Christian" uniqKey="Wolfram C" first="Christian" last="Wolfram">Christian Wolfram</name><affiliation><nlm:aff id="Aff7">Department of Ophthalmology, J. Gutenberg University Medical Center, Mainz, Germany</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="Aff7">Department of Ophthalmology, J. Gutenberg University Medical Center, Mainz, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="Aff37">Institute of Clinical Chemistry and Laboratory Medicine, J. Gutenberg University Medical Center, Mainz, Germany</nlm:aff></affiliation></author><author><name sortKey="Tonjes, Anke" sort="Tonjes, Anke" uniqKey="Tonjes A" first="Anke" last="Tönjes">Anke Tönjes</name><affiliation><nlm:aff id="Aff38">Department of Medicine, University of Leipzig, Leipzig, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="Aff39">Integrated Research and Treatment Center (IFB) AdiposityDiseases, University of Leipzig, Leipzig, Germany</nlm:aff></affiliation></author><author><name sortKey="M Gi, Reedik" sort="M Gi, Reedik" uniqKey="M Gi R" first="Reedik" last="M Gi">Reedik M Gi</name><affiliation><nlm:aff id="Aff40">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="Aff41">The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Lehtim Ki, Terho" sort="Lehtim Ki, Terho" uniqKey="Lehtim Ki T" first="Terho" last="Lehtim Ki">Terho Lehtim Ki</name><affiliation><nlm:aff id="Aff42">Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="Aff43">University of Tampere School of Medicine, Tampere, Finland</nlm:aff></affiliation></author><author><name sortKey="K Honen, Mika" sort="K Honen, Mika" uniqKey="K Honen M" first="Mika" last="K Hönen">Mika K Hönen</name><affiliation><nlm:aff id="Aff44">Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="Aff45">Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland</nlm:aff></affiliation></author><author><name sortKey="Esko, T Nu" sort="Esko, T Nu" uniqKey="Esko T" first="T Nu" last="Esko">T Nu Esko</name><affiliation><nlm:aff id="Aff40">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Metspalu, Andres" sort="Metspalu, Andres" uniqKey="Metspalu A" first="Andres" last="Metspalu">Andres Metspalu</name><affiliation><nlm:aff id="Aff40">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Rantanen, Taina" sort="Rantanen, Taina" uniqKey="Rantanen T" first="Taina" last="Rantanen">Taina Rantanen</name><affiliation><nlm:aff id="Aff46">Department of Health Sciences, Gerontology Research Center, University of Jyväskylä, Jyväskylä, Finland</nlm:aff></affiliation></author><author><name sortKey="P Rssinen, Olavi" sort="P Rssinen, Olavi" uniqKey="P Rssinen O" first="Olavi" last="P Rssinen">Olavi P Rssinen</name><affiliation><nlm:aff id="Aff47">Department of Ophthalmology, Central Hospital of Central Finland, Jyväskylä, Finland</nlm:aff></affiliation></author><author><name sortKey="Klein, Barbara E" sort="Klein, Barbara E" uniqKey="Klein B" first="Barbara E." last="Klein">Barbara E. Klein</name><affiliation><nlm:aff id="Aff48">Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, USA</nlm:aff></affiliation></author><author><name sortKey="Meitinger, Thomas" sort="Meitinger, Thomas" uniqKey="Meitinger T" first="Thomas" last="Meitinger">Thomas Meitinger</name><affiliation><nlm:aff id="Aff49">Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="Aff50">Institute of Human Genetics, Technical University Munich, Munich, Germany</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="Aff3">Department of Twin Research and Genetic Epidemiology, King’s College London, St. Thomas’ Hospital, London, UK</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="Aff51">Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Smith, Albert V" sort="Smith, Albert V" uniqKey="Smith A" first="Albert V." last="Smith">Albert V. Smith</name><affiliation><nlm:aff id="Aff52">Department of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="Aff53">Icelandic Heart Association, Kopavogur, Iceland</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="Aff63">Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff54">Department of Clinical and Molecular Ophthalmogenetics, Netherlands Institute of Neurosciences (NIN), An Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff55">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 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="Aff1">Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Eiriksd Ttir, Gu N" sort="Eiriksd Ttir, Gu N" uniqKey="Eiriksd Ttir G" first="Gu N" last="Eiríksd Ttir">Gu N Eiríksd Ttir</name><affiliation><nlm:aff id="Aff53">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name><affiliation><nlm:aff id="Aff52">Department of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="Aff53">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Doring, Angela" sort="Doring, Angela" uniqKey="Doring A" first="Angela" last="Döring">Angela Döring</name><affiliation><nlm:aff id="Aff64">Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Bettecken, Thomas" sort="Bettecken, Thomas" uniqKey="Bettecken T" first="Thomas" last="Bettecken">Thomas Bettecken</name><affiliation><nlm:aff id="Aff56">Center for Applied Genotyping, Max Planck Institute of Psychiatry, German Research Institute of Psychiatry, Munich, Germany</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff55">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Williams, Cathy" sort="Williams, Cathy" uniqKey="Williams C" first="Cathy" last="Williams">Cathy Williams</name><affiliation><nlm:aff id="Aff57">Centre for Child and Adolescent Health, University of Bristol, Bristol, 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="Aff58">Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Castagne, Raphaele" sort="Castagne, Raphaele" uniqKey="Castagne R" first="Raphaële" last="Castagné">Raphaële Castagné</name><affiliation><nlm:aff id="Aff59">INSERM UMRS 937, Pierre and Marie Curie University (UPMC, Paris 6) and Medical School, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Oexle, Konrad" sort="Oexle, Konrad" uniqKey="Oexle K" first="Konrad" last="Oexle">Konrad Oexle</name><affiliation><nlm:aff id="Aff50">Institute of Human Genetics, Technical University Munich, Munich, Germany</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="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Iyengar, Sudha K" sort="Iyengar, Sudha K" uniqKey="Iyengar S" first="Sudha K." last="Iyengar">Sudha K. Iyengar</name><affiliation><nlm:aff id="Aff16">Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, USA</nlm:aff></affiliation></author><author><name sortKey="Mitchell, Paul" sort="Mitchell, Paul" uniqKey="Mitchell P" first="Paul" last="Mitchell">Paul Mitchell</name><affiliation><nlm:aff id="Aff60">Department of Ophthalmology, Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Wang, Jie Jin" sort="Wang, Jie Jin" uniqKey="Wang J" first="Jie Jin" last="Wang">Jie Jin Wang</name><affiliation><nlm:aff id="Aff11">Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="Aff60">Department of Ophthalmology, Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Sydney, 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="Aff7">Department of Ophthalmology, J. Gutenberg University Medical Center, Mainz, Germany</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="Aff7">Department of Ophthalmology, J. Gutenberg University Medical Center, Mainz, Germany</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="Aff14">Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, USA</nlm:aff></affiliation></author><author><name sortKey="Stambolian, Dwight" sort="Stambolian, Dwight" uniqKey="Stambolian D" first="Dwight" last="Stambolian">Dwight Stambolian</name><affiliation><nlm:aff id="Aff61">Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA</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="Aff4">Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff5">Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="Aff15">Department of Ophthalmology, National University Health System, National University of Singapore, Singapore, Singapore</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="Aff3">Department of Twin Research and Genetic Epidemiology, King’s College London, St. Thomas’ Hospital, 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="Aff1">Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</nlm:aff></affiliation></author></analytic><series><title level="j">Human Genetics</title><idno type="ISSN">0340-6717</idno><idno type="eISSN">1432-1203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest <italic>P</italic> value 3.87 × 10<sup>−12</sup> for SNP rs634990 in Caucasians, and 9.65 × 10<sup>−4</sup> for rs8032019 in Asians. The overall meta-analysis provided <italic>P</italic> value 9.20 × 10<sup>−23</sup> for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, <italic>P</italic> < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, <italic>P</italic> < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (<italic>P</italic> value 5.81 × 10<sup>−2</sup> for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.</p><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1007/s00439-012-1176-0) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Baird, Pn" uniqKey="Baird P">PN Baird</name></author><author><name sortKey="Schache, M" uniqKey="Schache M">M Schache</name></author><author><name sortKey="Dirani, M" uniqKey="Dirani M">M Dirani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Curtin, Bj" uniqKey="Curtin B">BJ Curtin</name></author><author><name sortKey="Karlin, Db" uniqKey="Karlin D">DB Karlin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deans, Mr" uniqKey="Deans M">MR Deans</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Hum Genet</journal-id><journal-id journal-id-type="iso-abbrev">Hum. Genet</journal-id><journal-title-group><journal-title>Human Genetics</journal-title></journal-title-group><issn pub-type="ppub">0340-6717</issn><issn pub-type="epub">1432-1203</issn><publisher><publisher-name>Springer-Verlag</publisher-name><publisher-loc>Berlin/Heidelberg</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22665138</article-id><article-id pub-id-type="pmc">3418496</article-id><article-id pub-id-type="publisher-id">1176</article-id><article-id pub-id-type="doi">10.1007/s00439-012-1176-0</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Investigation</subject></subj-group></article-categories><title-group><article-title>Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. 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W.</given-names></name><address><phone>+31-651934491</phone><fax>+31-10-7044657</fax><email>c.c.w.klaver@erasmusmc.nl</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><aff id="Aff1"><label>1</label>Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</aff><aff id="Aff2"><label>2</label>Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands</aff><aff id="Aff3"><label>3</label>Department of Twin Research and Genetic Epidemiology, King’s College London, St. Thomas’ Hospital, London, UK</aff><aff id="Aff4"><label>4</label>Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore</aff><aff id="Aff5"><label>5</label>Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore</aff><aff id="Aff6"><label>6</label>Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</aff><aff id="Aff7"><label>7</label>Department of Ophthalmology, J. Gutenberg University Medical Center, Mainz, Germany</aff><aff id="Aff8"><label>8</label>School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK</aff><aff id="Aff9"><label>9</label>Division of Epidemiology and Clinical Applications, National Eye Institute, Intramural Research Program, National Institutes of Health, Bethesda, USA</aff><aff id="Aff10"><label>10</label>Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan</aff><aff id="Aff11"><label>11</label>Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia</aff><aff id="Aff12"><label>12</label>Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia</aff><aff id="Aff13"><label>13</label>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA</aff><aff id="Aff14"><label>14</label>Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, USA</aff><aff id="Aff15"><label>15</label>Department of Ophthalmology, National University Health System, National University of Singapore, Singapore, Singapore</aff><aff id="Aff16"><label>16</label>Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, USA</aff><aff id="Aff17"><label>17</label>Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore</aff><aff id="Aff18"><label>18</label>Center for Human Genetics, Duke University Medical Center, Durham, USA</aff><aff id="Aff19"><label>19</label>Department of Medicine, National University of Singapore, Singapore, Singapore</aff><aff id="Aff20"><label>20</label>Duke-National University of Singapore Graduate Medical School, Singapore, Singapore</aff><aff id="Aff21"><label>21</label>Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore</aff><aff id="Aff22"><label>22</label>Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore</aff><aff id="Aff23"><label>23</label>Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</aff><aff id="Aff24"><label>24</label>Faculty of Medicine, University of Split, Split, Croatia</aff><aff id="Aff25"><label>25</label>Princess Alexandra Eye Pavilion, Edinburgh, UK</aff><aff id="Aff26"><label>26</label>Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan</aff><aff id="Aff27"><label>27</label>Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan</aff><aff id="Aff28"><label>28</label>School of Social and Community Medicine, University of Bristol, Bristol, UK</aff><aff id="Aff29"><label>29</label>Department of Genetics and Population Health, Queensland Institute of Medical Research, Brisbane, Australia</aff><aff id="Aff30"><label>30</label>Medical Research Council Centre of Epidemiology for Child Health, Institute of Child Health, University College London, London, UK</aff><aff id="Aff31"><label>31</label>Institute of Ophthalmology, University College London, London, UK</aff><aff id="Aff32"><label>32</label>Ulverscroft Vision Research Group, University College London, London, UK</aff><aff id="Aff33"><label>33</label>Department of Neurology, Boston University School of Medicine, Boston, USA</aff><aff id="Aff34"><label>34</label>Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, USA</aff><aff id="Aff35"><label>35</label>Institute of Population Genetics, National Research Council, Sassari, Italy</aff><aff id="Aff36"><label>36</label>Glaucoma Service, The Rotterdam Eye Hospital, Rotterdam, The Netherlands</aff><aff id="Aff37"><label>37</label>Institute of Clinical Chemistry and Laboratory Medicine, J. Gutenberg University Medical Center, Mainz, Germany</aff><aff id="Aff38"><label>38</label>Department of Medicine, University of Leipzig, Leipzig, Germany</aff><aff id="Aff39"><label>39</label>Integrated Research and Treatment Center (IFB) AdiposityDiseases, University of Leipzig, Leipzig, Germany</aff><aff id="Aff40"><label>40</label>Estonian Genome Center, University of Tartu, Tartu, Estonia</aff><aff id="Aff41"><label>41</label>The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK</aff><aff id="Aff42"><label>42</label>Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland</aff><aff id="Aff43"><label>43</label>University of Tampere School of Medicine, Tampere, Finland</aff><aff id="Aff44"><label>44</label>Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland</aff><aff id="Aff45"><label>45</label>Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland</aff><aff id="Aff46"><label>46</label>Department of Health Sciences, Gerontology Research Center, University of Jyväskylä, Jyväskylä, Finland</aff><aff id="Aff47"><label>47</label>Department of Ophthalmology, Central Hospital of Central Finland, Jyväskylä, Finland</aff><aff id="Aff48"><label>48</label>Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, USA</aff><aff id="Aff49"><label>49</label>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany</aff><aff id="Aff50"><label>50</label>Institute of Human Genetics, Technical University Munich, Munich, Germany</aff><aff id="Aff51"><label>51</label>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</aff><aff id="Aff52"><label>52</label>Department of Medicine, University of Iceland, Reykjavik, Iceland</aff><aff id="Aff53"><label>53</label>Icelandic Heart Association, Kopavogur, Iceland</aff><aff id="Aff54"><label>54</label>Department of Clinical and Molecular Ophthalmogenetics, Netherlands Institute of Neurosciences (NIN), An Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands</aff><aff id="Aff55"><label>55</label>Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</aff><aff id="Aff56"><label>56</label>Center for Applied Genotyping, Max Planck Institute of Psychiatry, German Research Institute of Psychiatry, Munich, Germany</aff><aff id="Aff57"><label>57</label>Centre for Child and Adolescent Health, University of Bristol, Bristol, UK</aff><aff id="Aff58"><label>58</label>Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany</aff><aff id="Aff59"><label>59</label>INSERM UMRS 937, Pierre and Marie Curie University (UPMC, Paris 6) and Medical School, Paris, France</aff><aff id="Aff60"><label>60</label>Department of Ophthalmology, Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia</aff><aff id="Aff61"><label>61</label>Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA</aff><aff id="Aff63"><label>63</label>Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands</aff><aff id="Aff64"><label>64</label>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Neuherberg, Germany</aff></contrib-group><pub-date pub-type="epub"><day>5</day><month>6</month><year>2012</year></pub-date><pub-date pub-type="pmc-release"><day>5</day><month>6</month><year>2012</year></pub-date><pub-date pub-type="ppub"><month>9</month><year>2012</year></pub-date><volume>131</volume><issue>9</issue><fpage>1467</fpage><lpage>1480</lpage><history><date date-type="received"><day>20</day><month>3</month><year>2012</year></date><date date-type="accepted"><day>27</day><month>4</month><year>2012</year></date></history><permissions><copyright-statement>© The Author(s) 2012</copyright-statement></permissions><abstract id="Abs1"><p>Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest <italic>P</italic> value 3.87 × 10<sup>−12</sup> for SNP rs634990 in Caucasians, and 9.65 × 10<sup>−4</sup> for rs8032019 in Asians. The overall meta-analysis provided <italic>P</italic> value 9.20 × 10<sup>−23</sup> for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, <italic>P</italic> < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, <italic>P</italic> < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (<italic>P</italic> value 5.81 × 10<sup>−2</sup> for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.</p><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1007/s00439-012-1176-0) contains supplementary material, which is available to authorized users.</p></sec></abstract><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© Springer-Verlag 2012</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec id="Sec1"><title>Introduction</title><p>Refractive errors are common optical defects of the visual system. An important refractive error is myopia (nearsightedness), which occurs when the eye elongates beyond the focal plane. The prevalence of myopia is high, affecting about one-third of the world’s population, and reaching over 70 % in certain Asian ethnic groups (He et al. <xref ref-type="bibr" rid="CR10">2004</xref>; Kempen et al. <xref ref-type="bibr" rid="CR15">2004</xref>; Lin et al. <xref ref-type="bibr" rid="CR19">2004</xref>; Vitale et al. <xref ref-type="bibr" rid="CR34">2008</xref>; Wu et al. <xref ref-type="bibr" rid="CR36">2001</xref>). High degrees of myopia are associated with pathologic ocular changes, such as myopic macular degeneration, retinal detachment, and glaucoma (Curtin and Karlin <xref ref-type="bibr" rid="CR2">1971</xref>; McBrien and Gentle <xref ref-type="bibr" rid="CR21">2003</xref>; Saw <xref ref-type="bibr" rid="CR27">2006</xref>; Saw et al. <xref ref-type="bibr" rid="CR29">2005</xref>; Tano <xref ref-type="bibr" rid="CR33">2002</xref>). Due to the limited treatment options, myopia is a common cause of visual impairment (Tano <xref ref-type="bibr" rid="CR33">2002</xref>; Young <xref ref-type="bibr" rid="CR37">2009</xref>).</p><p>Refractive errors, and myopia in particular, are complex genetic traits with a largely unknown etiology. Established environmental factors are education, early reading, and reduced outdoor exposure (Dirani et al. <xref ref-type="bibr" rid="CR4">2009</xref>; Ip et al. <xref ref-type="bibr" rid="CR12">2008</xref>; McBrien et al. <xref ref-type="bibr" rid="CR22">2008</xref>; Morgan and Rose <xref ref-type="bibr" rid="CR23">2005</xref>; Rose et al. <xref ref-type="bibr" rid="CR26">2008</xref>; Saw et al. <xref ref-type="bibr" rid="CR28">2001</xref>; Young <xref ref-type="bibr" rid="CR37">2009</xref>). Although heritability estimates are high [50–90 % (Young et al. <xref ref-type="bibr" rid="CR38">2007</xref>)], the search for myopia genes is still ongoing. Previous linkage and association studies have led to the identification of at least 18 myopia (MYP) loci, 10 additional chromosomal regions, and several candidate genes (Baird et al. <xref ref-type="bibr" rid="CR1">2010</xref>; Young <xref ref-type="bibr" rid="CR37">2009</xref>). Replication of these associations has been inconsistent, and their application to the general population is limited (Baird et al. <xref ref-type="bibr" rid="CR1">2010</xref>).</p><p>Recent genome-wide association studies (GWAS) reported several susceptibility loci for refractive error and myopia (Hysi et al. <xref ref-type="bibr" rid="CR11">2010</xref>; Li et al. <xref ref-type="bibr" rid="CR17">2011a</xref>, <xref ref-type="bibr" rid="CR18">b</xref>; Nakanishi et al. <xref ref-type="bibr" rid="CR24">2009</xref>; Shi et al. <xref ref-type="bibr" rid="CR30">2011</xref>; Solouki et al. <xref ref-type="bibr" rid="CR31">2010</xref>). Solouki et al. (<xref ref-type="bibr" rid="CR31">2010</xref>) and Hysi et al. (<xref ref-type="bibr" rid="CR11">2010</xref>) were the first to perform a GWAS in a general Caucasian population, and identified susceptibility loci on chromosomes 15q14 and 15q25, respectively. In both studies, carriers of single nucleotide polymorphism (SNP) rs634990 at 15q14 (OR 1.83, 95 % CI 1.42–2.36) and of SNP rs8027411 at 15q25 (OR 1.16, 95 % CI 1.02–1.28) had a higher risk of myopia. Confirmation of these findings was obtained in various replication studies (Hayashi et al. <xref ref-type="bibr" rid="CR9">2011</xref>; Hysi et al. <xref ref-type="bibr" rid="CR11">2010</xref>; Solouki et al. <xref ref-type="bibr" rid="CR31">2010</xref>). However, these replication cohorts were relatively limited in size, increasing the chance of a type 1 error.</p><p>To address potential inaccuracies and to investigate generalizability, we investigated the associations between refractive error, and the 15q14 and 15q25 susceptibility loci in a large international replication and meta-analysis study (Consortium of Refractive Error and Myopia, CREAM) including 31 cohorts with various ethnicities from 4 different continents.</p></sec><sec id="Sec2" sec-type="results"><title>Results</title><sec id="Sec3"><title>Meta-analysis of allelic effects on spherical equivalent (SE)</title><p>Complete data on refractive error and genome-wide SNPs were available in all 29 population-based studies comprising 49,364 subjects: 42,224 Caucasians and 7,140 Asians (Table <xref rid="Tab1" ref-type="table">1</xref>; Fig. <xref rid="Fig1" ref-type="fig">1</xref>, Supplementary Table 1). This includes the previously reported discovery set consisting of 15,608 (Solouki et al. <xref ref-type="bibr" rid="CR31">2010</xref>) and 17,608 subjects (Hysi et al. <xref ref-type="bibr" rid="CR11">2010</xref>), respectively.<table-wrap id="Tab1"><label>Table 1</label><caption><p>Descriptives of all study cohorts</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left">Study</th><th align="left"><italic>n</italic></th><th align="left">Mean age (SD)</th><th align="left">Age range</th><th align="left">Men (%)</th><th align="left">Mean SE (SD)</th></tr></thead><tbody><tr><td align="left">1958 British Birth Cohort</td><td char="." align="char">1,658</td><td align="left">42 (0.0)</td><td align="left">40–50</td><td align="left">54.2</td><td align="left">−0.96 (2.00)</td></tr><tr><td align="left">AGES Reykjavik</td><td char="." align="char">2,986</td><td align="left">76.3 (5.4)</td><td align="left">60–80+</td><td align="left">35.3</td><td align="left">1.22 (2.05)</td></tr><tr><td align="left">ALSPAC</td><td char="." align="char">3,804</td><td align="left">15.4 (0.3)</td><td align="left">14.25–17.08</td><td align="left">47.2</td><td align="left">−0.38 (1.28)</td></tr><tr><td align="left">AREDS 1</td><td char="." align="char">816</td><td align="left">79.5 (5.1)</td><td align="left">60–80+</td><td align="left">43.5</td><td align="left">0.68 (1.94)</td></tr><tr><td align="left">AREDS 2</td><td char="." align="char">1,506</td><td align="left">68.0 (4.7)</td><td align="left">55–81</td><td align="left">41.1</td><td align="left">0.54 (2.25)</td></tr><tr><td align="left">Australian Twins</td><td char="." align="char">1,819</td><td align="left">22.2 (12.7)</td><td align="left">5–90</td><td align="left">44.0</td><td align="left">−0.22 (1.28)</td></tr><tr><td align="left">Blue Mountains Eye Study</td><td char="." align="char">1,574</td><td align="left">64 (7.9)</td><td align="left">50–80+</td><td align="left">43.4</td><td align="left">0.59 (1.96)</td></tr><tr><td align="left">Croatia Split</td><td char="." align="char">366</td><td align="left">49.8 (14.4)</td><td align="left">18–85</td><td align="left">46.0</td><td align="left">−1.83 (1.83)</td></tr><tr><td align="left">Croatia Vis Island</td><td char="." align="char">544</td><td align="left">55.8 (14.0)</td><td align="left">18–83</td><td align="left">40.0</td><td align="left">−0.16 (1.93)</td></tr><tr><td align="left">Croatia Korcula Island</td><td char="." align="char">836</td><td align="left">56.0 (13.8)</td><td align="left">18–98</td><td align="left">35.0</td><td align="left">−0.25 (1.92)</td></tr><tr><td align="left">ERF</td><td char="." align="char">2,032</td><td align="left">48.5 (14.3)</td><td align="left">18+</td><td align="left">43.1</td><td align="left">0.07 (2.13)</td></tr><tr><td align="left">EGCUT</td><td char="." align="char">338</td><td align="left">34.8 (15.2)</td><td align="left">18–85</td><td align="left">36.9</td><td align="left">−2.60 (2.00)</td></tr><tr><td align="left">Finnish Twin Study on Aging</td><td char="." align="char">127</td><td align="left">68.2 (3.8)</td><td align="left">63–76</td><td align="left">0.0</td><td align="left">1.68 (1.54)</td></tr><tr><td align="left">Framingham Eye Study</td><td char="." align="char">1,500</td><td align="left">55.5 (9.0)</td><td align="left">20–80</td><td align="left">42.5</td><td align="left">−0.17 (2.40)</td></tr><tr><td align="left">Gutenberg Health Study I</td><td char="." align="char">2,745</td><td align="left">55.7 (11)</td><td align="left">35–74</td><td align="left">51.5</td><td align="left">−0.38 (2.44)</td></tr><tr><td align="left">Gutenberg Health Study II</td><td char="." align="char">1,142</td><td align="left">55.0 (10.9)</td><td align="left">35–74</td><td align="left">49.8</td><td align="left">−0.41 (2.58)</td></tr><tr><td align="left">KORA</td><td char="." align="char">1,867</td><td align="left">55.6 (11.7)</td><td align="left">35–84</td><td align="left">49.6</td><td align="left">−0.29 (2.27)</td></tr><tr><td align="left">MESA</td><td char="." align="char">1,462</td><td align="left">62 (9.4)</td><td align="left">46–86</td><td align="left">49.5</td><td align="left">−0.28 (2.62)</td></tr><tr><td align="left">ORCADES</td><td char="." align="char">505</td><td align="left">54.8 (13.7)</td><td align="left">22–88.5</td><td align="left">43.0</td><td align="left">0.01 (2.14)</td></tr><tr><td align="left">Rotterdam Study 1</td><td char="." align="char">5,328</td><td align="left">68.5 (8.6)</td><td align="left">55+</td><td align="left">41.3</td><td align="left">0.86 (2.45)</td></tr><tr><td align="left">Rotterdam Study 2</td><td char="." align="char">2,009</td><td align="left">64.2 (7.4)</td><td align="left">55+</td><td align="left">45.9</td><td align="left">0.48 (2.51)</td></tr><tr><td align="left">Rotterdam Study 3</td><td char="." align="char">1,970</td><td align="left">56.0 (5.5)</td><td align="left">45+</td><td align="left">43.9</td><td align="left">−0.35 (2.62)</td></tr><tr><td align="left">OGP Talana</td><td char="." align="char">623</td><td align="left">44.5 (21.1)</td><td align="left">5–89</td><td align="left">51.8</td><td align="left">−0.15 (1.78)</td></tr><tr><td align="left">SCORM</td><td char="." align="char">929</td><td align="left">10.8 (0.8)</td><td align="left">10–15</td><td align="left">48.0</td><td align="left">−2.02 (2.26)</td></tr><tr><td align="left">SiMES</td><td char="." align="char">2,226</td><td align="left">57.7 (10.8)</td><td align="left">40–80</td><td align="left">49.3</td><td align="left">−0.08 (1.98)</td></tr><tr><td align="left">SINDI</td><td char="." align="char">2,055</td><td align="left">55.7 (8.7)</td><td align="left">40–80+</td><td align="left">51.2</td><td align="left">0.01 (2.13)</td></tr><tr><td align="left">SP2</td><td char="." align="char">1,930</td><td align="left">47.5 (10.9)</td><td align="left">20–80</td><td align="left">45.4</td><td align="left">−1.67 (2.89)</td></tr><tr><td align="left">TwinsUK</td><td char="." align="char">4,270</td><td align="left">55.0 (12.0)</td><td align="left">20–82</td><td align="left">7.4</td><td align="left">−0.39 (2.73)</td></tr><tr><td align="left">Young Finns</td><td char="." align="char">397</td><td align="left">37.6 (5.2)</td><td align="left">25–50</td><td align="left">45.0</td><td align="left">−1.20 (2.29)</td></tr><tr><td align="left">Kyoto Study</td><td char="." align="char">5,192</td><td align="left">na</td><td align="left">na</td><td align="left">na</td><td align="left">na</td></tr><tr><td align="left"> Cases</td><td char="." align="char">1,143</td><td align="left">58.4 (14.3)</td><td align="left">20–91</td><td align="left">33.3</td><td align="left">−10.50 (6.44)</td></tr><tr><td align="left"> Controls 1</td><td char="." align="char">3,120</td><td align="left">58.5 (13.6)</td><td align="left">20–90</td><td align="left">61.7</td><td align="left">na</td></tr><tr><td align="left"> Controls 2</td><td char="." align="char">929</td><td align="left">38.8 (11.8)</td><td align="left">0–74</td><td align="left">41.3</td><td align="left">na</td></tr><tr><td align="left">SORBS</td><td char="." align="char">621</td><td align="left">na</td><td align="left">na</td><td align="left">na</td><td align="left">na</td></tr><tr><td align="left"> Cases</td><td char="." align="char">100</td><td align="left">45.4 (6.6)</td><td align="left">18–40</td><td align="left">36.4</td><td align="left">na</td></tr><tr><td align="left"> Controls</td><td char="." align="char">521</td><td align="left">28.3 (15.16)</td><td align="left">18–80</td><td align="left">45.0</td><td align="left">na</td></tr></tbody></table></table-wrap><fig id="Fig1"><label>Fig. 1</label><caption><p>Mean age and distribution of spherical equivalent in all study cohorts</p></caption><graphic xlink:href="439_2012_1176_Fig1_HTML" id="MO1"></graphic></fig></p><p>Table <xref rid="Tab2" ref-type="table">2</xref> shows the results of the meta-analysis of the 14 SNPs (Hysi et al. <xref ref-type="bibr" rid="CR11">2010</xref>; Solouki et al. <xref ref-type="bibr" rid="CR31">2010</xref>) at locus 15q14 and 5 SNPs at locus 15q25. The frequency of the effect allele C for top SNP rs634990 at locus 15q14 ranged from 0.38 to 0.64, while frequency of the effect allele A for top SNP rs939661 at 15q25 showed a larger variation, ranging from 0.28 to 0.63 (Supplementary Figure 1). The sample size of each SNP per study is provided in Supplementary Table 1. For locus 15q14, the magnitude and direction of the effects were consistent in all cohorts except Croatia Vis and SIMES. For locus 15q25, there was less consistency; for top SNP rs939661 8 cohorts—both Caucasian and Asian (Australian Twins, Croatia Split, Croatia Vis, EGCUT, FITSA, GHS II, ORCADES, and SIMES)—had a regression beta coefficient in the opposite direction to that of the other studies.<table-wrap id="Tab2"><label>Table 2</label><caption><p>Meta-analysis of allelic effects on spherical equivalent at locus 15q14 and 15q25</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2">SNP</th><th align="left" rowspan="2">Position</th><th align="left" rowspan="2">Effect allele</th><th align="left" rowspan="2">Non effect allele</th><th align="left" rowspan="2">Freq.</th><th align="left" colspan="3">Discovery (<italic>n</italic> = 15,608)<sup>a</sup></th><th align="left" colspan="3">Replication (<italic>n</italic> = 33,755)<sup>b</sup></th><th align="left" colspan="3">Caucasian (<italic>n</italic> = 26,615)<sup>c</sup></th></tr><tr><th align="left">beta</th><th align="left">se</th><th align="left"><italic>P</italic></th><th align="left">beta</th><th align="left">se</th><th align="left"><italic>P</italic></th><th align="left">beta</th><th align="left">se</th><th align="left"><italic>P</italic></th></tr></thead><tbody><tr><td align="left" colspan="14"><italic>Locus 15q14</italic></td></tr><tr><td align="left">rs634990</td><td align="left">32793365</td><td align="left">C</td><td align="left">T</td><td align="left">0.49</td><td align="left">−0.23</td><td align="left">0.03</td><td align="left">1.35 x 10<sup>−14</sup></td><td align="left">−0.09</td><td align="left">0.01</td><td align="left">4.53 x 10<sup>−14</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">3.87 x 10<sup>−12</sup></td></tr><tr><td align="left">rs560766</td><td align="left">32788234</td><td align="left">A</td><td align="left">G</td><td align="left">0.48</td><td align="left">−0.20</td><td align="left">0.03</td><td align="left">4.82 x 10<sup>−12</sup></td><td align="left">−0.09</td><td align="left">0.01</td><td align="left">3.53 x 10<sup>−14</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">3.91 x 10<sup>−12</sup></td></tr><tr><td align="left">rs524952</td><td align="left">32793178</td><td align="left">A</td><td align="left">T</td><td align="left">0.48</td><td align="left">−0.23</td><td align="left">0.03</td><td align="left">1.19 x 10<sup>−14</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">9.05 x 10<sup>−13</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">1.07 x 10<sup>−11</sup></td></tr><tr><td align="left">rs688220</td><td align="left">32786167</td><td align="left">A</td><td align="left">G</td><td align="left">0.48</td><td align="left">−0.20</td><td align="left">0.03</td><td align="left">4.43 x 10<sup>−12</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">1.01 x 10<sup>−13</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">1.38 x 10<sup>−11</sup></td></tr><tr><td align="left">rs580839</td><td align="left">32786121</td><td align="left">A</td><td align="left">G</td><td align="left">0.48</td><td align="left">−0.20</td><td align="left">0.03</td><td align="left">4.39 x 10<sup>−12</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">1.05 x 10<sup>−13</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">1.34 x 10<sup>−11</sup></td></tr><tr><td align="left">rs11073060</td><td align="left">32777143</td><td align="left">A</td><td align="left">C</td><td align="left">0.48</td><td align="left">−0.21</td><td align="left">0.03</td><td align="left">1.12 x 10<sup>−12</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">2.46 x 10<sup>−13</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">2.47 x 10<sup>−11</sup></td></tr><tr><td align="left">rs4924134</td><td align="left">32781857</td><td align="left">G</td><td align="left">A</td><td align="left">0.45</td><td align="left">−0.21</td><td align="left">0.03</td><td align="left">1.20 x 10<sup>−12</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">3.01 x 10<sup>−13</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">2.96 x 10<sup>−11</sup></td></tr><tr><td align="left">rs7176510</td><td align="left">32786771</td><td align="left">T</td><td align="left">C</td><td align="left">0.45</td><td align="left">−0.20</td><td align="left">0.03</td><td align="left">1.70 x 10<sup>−11</sup></td><td align="left">−0.09</td><td align="left">0.01</td><td align="left">8.31 x 10<sup>−14</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">7.81 x 10<sup>−12</sup></td></tr><tr><td align="left">rs619788</td><td align="left">32782398</td><td align="left">A</td><td align="left">C</td><td align="left">0.44</td><td align="left">−0.20</td><td align="left">0.03</td><td align="left">3.94 x 10<sup>−12</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">2.21 x 10<sup>−13</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">2.29 x 10<sup>−11</sup></td></tr><tr><td align="left">rs7163001</td><td align="left">32777866</td><td align="left">A</td><td align="left">G</td><td align="left">0.44</td><td align="left">−0.21</td><td align="left">0.03</td><td align="left">1.26 x 10<sup>−12</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">6.28 x 10<sup>−13</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">4.16 x 10<sup>−11</sup></td></tr><tr><td align="left">rs11073059</td><td align="left">32776966</td><td align="left">A</td><td align="left">T</td><td align="left">0.44</td><td align="left">−0.21</td><td align="left">0.03</td><td align="left">1.98 x 10<sup>−12</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">8.78 x 10<sup>−13</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">4.85 x 10<sup>−11</sup></td></tr><tr><td align="left">rs11073058</td><td align="left">32776918</td><td align="left">T</td><td align="left">G</td><td align="left">0.44</td><td align="left">−0.20</td><td align="left">0.03</td><td align="left">2.23 x 10<sup>−12</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">8.52 x 10<sup>−13</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">4.84 x 10<sup>−11</sup></td></tr><tr><td align="left">rs685352</td><td align="left">32795627</td><td align="left">G</td><td align="left">A</td><td align="left">0.46</td><td align="left">−0.21</td><td align="left">0.03</td><td align="left">4.55 x 10<sup>−13</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">4.32 x 10<sup>−12</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">2.09 x 10<sup>−10</sup></td></tr><tr><td align="left">rs8032019</td><td align="left">32778782</td><td align="left">G</td><td align="left">A</td><td align="left">0.40</td><td align="left">−0.19</td><td align="left">0.03</td><td align="left">1.00 x 10<sup>−10</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">5.81 x 10<sup>−12</sup></td><td align="left">−0.08</td><td align="left">0.01</td><td align="left">7.00 x 10<sup>−10</sup></td></tr></tbody></table><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2">SNP</th><th align="left" rowspan="2">Position</th><th align="left" rowspan="2">Effect allele</th><th align="left" rowspan="2">Non effect allele</th><th align="left" rowspan="2">Freq.</th><th align="left" colspan="3">Discovery (<italic>n</italic> = 17,806)<sup>a</sup></th><th align="left" colspan="3">Replication (<italic>n</italic> = 31,557)<sup>b</sup> </th><th align="left" colspan="3">Caucasian (<italic>n</italic> = 24,417)<sup>c</sup> </th></tr><tr><th align="left">beta</th><th align="left">se</th><th align="left"><italic>P</italic></th><th align="left">beta</th><th align="left">se</th><th align="left"><italic>P</italic></th><th align="left">beta</th><th align="left">se</th><th align="left"><italic>P</italic></th></tr></thead><tbody><tr><td align="left" colspan="5"><italic>Locus 15q25</italic></td><td align="left" colspan="3"></td><td align="left" colspan="3"></td><td align="left" colspan="3"></td></tr><tr><td align="left">rs939661</td><td align="left">77218118</td><td align="left">A</td><td align="left">G</td><td align="left">0.51</td><td align="left">−0.15</td><td align="left">0.03</td><td align="left">3.85 x 10<sup>−9</sup></td><td align="left">−0.02</td><td align="left">0.01</td><td align="left">5.81 x 10<sup>−2</sup></td><td align="left">−0.02</td><td align="left">0.01</td><td align="left">7.73 x 10<sup>−2</sup></td></tr><tr><td align="left">rs939658</td><td align="left">77238924</td><td align="left">G</td><td align="left">A</td><td align="left">0.51</td><td align="left">−0.15</td><td align="left">0.03</td><td align="left">1.85 x 10<sup>−9</sup></td><td align="left">−0.02</td><td align="left">0.01</td><td align="left">1.60 x 10<sup>−1</sup></td><td align="left">−0.02</td><td align="left">0.01</td><td align="left">2.16 x 10<sup>−1</sup></td></tr><tr><td align="left">rs17175798</td><td align="left">77251015</td><td align="left">C</td><td align="left">T</td><td align="left">0.51</td><td align="left">−0.15</td><td align="left">0.03</td><td align="left">1.99 x 10<sup>−9</sup></td><td align="left">−0.02</td><td align="left">0.01</td><td align="left">1.81 x 10<sup>−1</sup></td><td align="left">−0.01</td><td align="left">0.01</td><td align="left">2.38 x 10<sup>−1</sup></td></tr><tr><td align="left">rs8033963</td><td align="left">77242405</td><td align="left">C</td><td align="left">C</td><td align="left">0.51</td><td align="left">−0.15</td><td align="left">0.03</td><td align="left">1.86 x 10<sup>−9</sup></td><td align="left">−0.01</td><td align="left">0.01</td><td align="left">2.18 x 10<sup>−1</sup></td><td align="left">−0.02</td><td align="left">0.01</td><td align="left">2.20 x 10<sup>−1</sup></td></tr><tr><td align="left">rs8027411</td><td align="left">77248084</td><td align="left">T</td><td align="left">G</td><td align="left">0.51</td><td align="left">−0.15</td><td align="left">0.03</td><td align="left">2.07 x 10<sup>−9</sup></td><td align="left">−0.01</td><td align="left">0.01</td><td align="left">2.49 x 10<sup>−1</sup></td><td align="left">−0.02</td><td align="left">0.01</td><td align="left">2.16 x 10<sup>−1</sup></td></tr></tbody></table><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2">SNP</th><th align="left" rowspan="2">Position</th><th align="left" rowspan="2">Effect allele</th><th align="left" rowspan="2">Non effect allele</th><th align="left" rowspan="2">Freq.</th><th align="left" colspan="3">Asian (<italic>n</italic> = 7,140)<sup>d</sup></th><th align="left" colspan="3">Meta-analysis (<italic>n</italic> = 49,363)<sup>e</sup></th></tr><tr><th align="left">beta</th><th align="left">se</th><th align="left"><italic>P</italic></th><th align="left">beta</th><th align="left">se</th><th align="left"><italic>P</italic></th></tr></thead><tbody><tr><td align="left" colspan="11"><italic>Locus 15q14</italic></td></tr><tr><td align="left">rs634990</td><td align="left">32793365</td><td align="left">C</td><td align="left">T</td><td align="left">0.49</td><td align="left">−0.12</td><td align="left">0.04</td><td align="left">2.21 x 10<sup>−3</sup></td><td align="left">−0.11</td><td align="left">0.01</td><td align="left">9.20 x 10<sup>−3</sup></td></tr><tr><td align="left">rs560766</td><td align="left">32788234</td><td align="left">A</td><td align="left">G</td><td align="left">0.48</td><td align="left">−0.12</td><td align="left">0.04</td><td align="left">1.47 x 10<sup>−3</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">1.03 x 10<sup>−21</sup></td></tr><tr><td align="left">rs524952</td><td align="left">32793178</td><td align="left">A</td><td align="left">T</td><td align="left">0.48</td><td align="left">−0.18</td><td align="left">0.07</td><td align="left">9.52 x 10<sup>−3</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">2.00 x 10<sup>−21</sup></td></tr><tr><td align="left">rs688220</td><td align="left">32786167</td><td align="left">A</td><td align="left">G</td><td align="left">0.48</td><td align="left">−0.12</td><td align="left">0.04</td><td align="left">9.80 x 10<sup>−4</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">3.44 x 10<sup>−21</sup></td></tr><tr><td align="left">rs580839</td><td align="left">32786121</td><td align="left">A</td><td align="left">G</td><td align="left">0.48</td><td align="left">−0.12</td><td align="left">0.04</td><td align="left">1.10 x 10<sup>−3</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">3.51 x 10<sup>−21</sup></td></tr><tr><td align="left">rs11073060</td><td align="left">32777143</td><td align="left">A</td><td align="left">C</td><td align="left">0.48</td><td align="left">−0.12</td><td align="left">0.04</td><td align="left">1.45 x 10<sup>−3</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">5.13 x 10<sup>−21</sup></td></tr><tr><td align="left">rs4924134</td><td align="left">32781857</td><td align="left">G</td><td align="left">A</td><td align="left">0.45</td><td align="left">−0.12</td><td align="left">0.04</td><td align="left">1.60 x 10<sup>−3</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">5.57 x 10<sup>−21</sup></td></tr><tr><td align="left">rs7176510</td><td align="left">32786771</td><td align="left">T</td><td align="left">C</td><td align="left">0.45</td><td align="left">−0.12</td><td align="left">0.04</td><td align="left">1.74 x 10<sup>−3</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">6.09 x 10<sup>−21</sup></td></tr><tr><td align="left">rs619788</td><td align="left">32782398</td><td align="left">A</td><td align="left">C</td><td align="left">0.44</td><td align="left">−0.12</td><td align="left">0.04</td><td align="left">1.54 x 10<sup>−3</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">6.97 x 10<sup>−21</sup></td></tr><tr><td align="left">rs7163001</td><td align="left">32777866</td><td align="left">A</td><td align="left">G</td><td align="left">0.44</td><td align="left">−0.11</td><td align="left">0.04</td><td align="left">2.81 x 10<sup>−3</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">1.41 x 10<sup>−20</sup></td></tr><tr><td align="left">rs11073059</td><td align="left">32776966</td><td align="left">A</td><td align="left">T</td><td align="left">0.44</td><td align="left">−0.11</td><td align="left">0.04</td><td align="left">3.64 x 10<sup>−3</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">2.63 x 10<sup>−20</sup></td></tr><tr><td align="left">rs11073058</td><td align="left">32776918</td><td align="left">T</td><td align="left">G</td><td align="left">0.44</td><td align="left">−0.11</td><td align="left">0.04</td><td align="left">3.50 x 10<sup>−3</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">2.68 x 10<sup>−20</sup></td></tr><tr><td align="left">rs685352</td><td align="left">32795627</td><td align="left">G</td><td align="left">A</td><td align="left">0.46</td><td align="left">−0.11</td><td align="left">0.04</td><td align="left">4.14 x 10<sup>−3</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">8.10 x 10<sup>−20</sup></td></tr><tr><td align="left">rs8032019</td><td align="left">32778782</td><td align="left">G</td><td align="left">A</td><td align="left">0.40</td><td align="left">−0.13</td><td align="left">0.04</td><td align="left">9.65 x 10<sup>−4</sup></td><td align="left">−0.10</td><td align="left">0.01</td><td align="left">1.78 x 10<sup>−18</sup></td></tr><tr><td align="left" colspan="11"><italic>Locus 15q25</italic></td></tr><tr><td align="left">rs939661</td><td align="left">77218118</td><td align="left">A</td><td align="left">G</td><td align="left">0.51</td><td char="." align="char">−0.03</td><td align="left">0.04</td><td align="left">4.86 x 10<sup>−1</sup></td><td align="left">−0.04</td><td align="left">0.01</td><td align="left">1.22 x 10<sup>−4</sup></td></tr><tr><td align="left">rs939658</td><td align="left">77238924</td><td align="left">G</td><td align="left">A</td><td align="left">0.51</td><td char="." align="char">−0.04</td><td align="left">0.05</td><td align="left">3.94 x 10<sup>−1</sup></td><td align="left">−0.04</td><td align="left">0.01</td><td align="left">4.32 x 10<sup>−4</sup></td></tr><tr><td align="left">rs17175798</td><td align="left">77251015</td><td align="left">C</td><td align="left">T</td><td align="left">0.51</td><td char="." align="char">−0.05</td><td align="left">0.06</td><td align="left">3.70 x 10<sup>−1</sup></td><td align="left">−0.04</td><td align="left">0.01</td><td align="left">6.12 x 10<sup>−4</sup></td></tr><tr><td align="left">rs8033963</td><td align="left">77242405</td><td align="left">C</td><td align="left">C</td><td align="left">0.51</td><td char="." align="char">−0.01</td><td align="left">0.04</td><td align="left">8.42 x 10<sup>−1</sup></td><td align="left">−0.04</td><td align="left">0.01</td><td align="left">9.37 x 10<sup>−4</sup></td></tr><tr><td align="left">rs8027411</td><td align="left">77248084</td><td align="left">T</td><td align="left">G</td><td align="left">0.51</td><td char="." align="char">0.00</td><td align="left">0.04</td><td align="left">9.12 x 10<sup>−1</sup></td><td align="left">−0.03</td><td align="left">0.01</td><td align="left">1.14 x 10<sup>−3</sup></td></tr></tbody></table><table-wrap-foot><p><italic>Freq</italic> average frequency</p><p><sup>a</sup>For the 15q14 locus: RS1, RS2, RS3, ERF, TwinsUK; for the 15q25 locus: TwinsUK, RS1, RS2, RS3, ERF, 1958 British Birth Cohort, Australian Twins (adult samples only)</p><p><sup>b</sup>For the 15q14 locus: 1958 British Birth Cohort, AGES, ALSPAC, AREDS 1, AREDS 2, Australian Twins, BMES, Croatia Split, Croatia Vis, Croatia Korcula, EGCUT, FITSA, Framingham, GHS I, GHS II, KORA, MESA, ORCADES, OGP Talana, SCORM, SiMES, SINDI, SP2, Young Finns; for the 15q25 locus: AGES, ALSPAC, AREDS 1, AREDS 2, BMES, Croatia Split, Croatia Vis, Croatia Korcula, EGCUT, FITSA, Framingham, GHS I, GHS II, KORA, MESA, ORCADES, OGP Talana, Young Finns, SCORM, SiMES, SINDI, SP2
</p><p><sup>c</sup>For the 15q14 locus: 1958 British Birth Cohort, AGES, ALSPAC, AREDS 1, AREDS 2, Australian Twins, BMES, Croatia Split, Croatia Vis, Croatia Korcula, EGCUT, FITSA, Framingham, GHS I, GHS II, KORA, MESA, ORCADES, OGP Talana, Young Finns; for 15q25 locus: AGES, ALSPAC, AREDS 1, AREDS 2, BMES, Croatia Split, Croatia Vis, Croatia Korcula, EGCUT, FITSA, Framingham, GHS I, GHS II, KORA, MESA, ORCADES, OGP Talana, Young Finns</p><p><sup>d</sup>Asian replication: SP2, SIMES, SINDI, SCORM</p><p><sup>e</sup>All studies</p></table-wrap-foot></table-wrap></p><p>For locus 15q14, the replication set, consisting of all studies except the ones previously used in the discovery analysis, showed a statistically significant association between SE and all SNPs with a best <italic>P</italic> value 4.53 × 10<sup>−14</sup> for top SNP rs634990. Confirmation was achieved in 23 out of 25 Caucasian studies (overall <italic>P</italic> 3.87 × 10<sup>−12</sup> for SNP rs634990), and in 3 out of 4 Asian studies (overall <italic>P</italic> 2.21 × 10<sup>−3</sup> for SNP rs634990). Meta-analysis of the discovery and replication cohorts together provided <italic>P</italic> value 9.20 × 10<sup>−23</sup> for SNP rs634990.</p><p>For locus 15q25, neither Caucasian nor Asian validation studies replicated the original association. Meta-analysis of the combined set of the 5 SNPs yielded a lowest <italic>P</italic> 1.22 × 10<sup>−4</sup> for SNP rs939661. As a subsequent analysis, we investigated locus 15q25 in more detail, and tested another 26 SNPs in 26 out of 29 cohorts (no data available in ALSPAC, AREDS 1, and EGCUT). This set of SNPs was not replicated either, however, meta-analysis including the discovery cohort was still significant (best <italic>P</italic> 2.07 × 10<sup>−4</sup> for SNP rs1915726; Supplementary Table 3).</p></sec><sec id="Sec4"><title>Meta-analysis of risk of myopia for top SNP</title><p>Genotype distributions for rs634990 at locus 15q14 were available for 28 out of 31 studies (all but FITSA, Australian Twins, and SORBS). There was no evidence of heterogeneity in the analyses of homozygote carriers [χ<sup>2</sup> 21.35 (d.f. 26), <italic>P</italic> 0.724, <italic>I</italic><sup>2</sup> 0.0 %] or heterozygote carriers [χ<sup>2</sup> 24.22 (d.f. 26), <italic>P</italic> 0.564, <italic>I</italic><sup>2</sup> 0.0 %]. Therefore, only results from fixed effects meta-analysis were used. Figure <xref rid="Fig2" ref-type="fig">2</xref> shows the forest plots for the risk of myopia for homozygous and heterozygous carriers of the top SNP rs634990. The OR of moderate to high myopia (SE ≤−3 D) versus moderate to high hyperopia (SE ≥+3 D) was 1.88 (95 % CI 1.64, 2.16, <italic>P</italic> < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and 1.33 (95 % CI 1.19, 1.49, <italic>P</italic> < 0.001) for heterozygous carriers.<fig id="Fig2"><label>Fig. 2</label><caption><p>Forest plots of odds ratios of myopia (spherical equivalent ≤−3 diopters) versus hyperopia (spherical equivalent ≥+3 diopters) for top SNP rs634990. *For studies without subjects with high or moderate hyperopia, emmetropia was used as a reference group. <bold>a</bold> Homozygotes carriers of alleles TT versus CC for SNP rs634990. <bold>b</bold> Heterozygotes carriers of alleles TT versus TC for SNP rs634990</p></caption><graphic xlink:href="439_2012_1176_Fig2_HTML" id="MO2"></graphic></fig></p></sec></sec><sec id="Sec5" sec-type="discussion"><title>Discussion</title><p>Chromosome 15q was first implicated in refractive error and myopia by genome-wide analysis of two large studies located in Northern Europe (Hysi et al. <xref ref-type="bibr" rid="CR11">2010</xref>; Solouki et al. <xref ref-type="bibr" rid="CR31">2010</xref>). Here, in an international meta-analysis consisting of 31 independent studies from the CREAM consortium, we provide further support that the association with locus 15q14 is robust and present in both Caucasians and Asians. We combined the results with those of the initial study into a powerful meta-analysis of highly associated SNPs with a total study population of 55,177 participants. The combined results showed that all tested SNPs for locus 15q14 were associated with refractive errors, and that homozygous carriers of the top SNP rs634990 had approximately twice the risk of myopia. SNPs at the other locus, 15q25, could not be convincingly replicated.</p><p>This study has strengths and limitations. Major strengths of the study include the sample size and the inclusion of different ethnicities. The CREAM consortium represents the largest study on refractive error known to date. Previous replication studies have not been large scaled and focused on populations of the same ancestry (Gao et al. <xref ref-type="bibr" rid="CR7">2012</xref>; Lu et al. <xref ref-type="bibr" rid="CR20">2011</xref>; Wang et al. <xref ref-type="bibr" rid="CR35">2011</xref>). Another advantage of our study is the incorporation of clinical relevant endpoints such as high myopia and high hyperopia. Among the limitations are differences in designs and methods of the studies. (1) Population-based as well as case control studies were incorporated. However, the latter were only two (Kyoto Study and SORBS) and both had results within the same range as the population-based studies. (2) Different types of equipment and measurement methods were used to detect refractive error. These differences are generally subtle, and are not likely to cause false findings. (3) Various methods of genotyping and imputation were used, and genotyping was not complete in all studies. All SNPs at 15q14 had similar effect; thus, we do not think this has influenced these associations. SNPs at 15q25 showed larger variation, and the incomplete genotyping may have underpowered this analysis.</p><p>Earlier replication of the 15q14 locus was reported by Hayashi et al. (<xref ref-type="bibr" rid="CR9">2011</xref>) in a Japanese sample of high myopic probands and controls. In a comparison of 1,125 high myopes (axial length >26.1 mm) versus 1,295 controls, the risk of high myopia was increased for the carriers of the initial top SNP rs634990 [OR 1.84 in homozygotes (95 % CI 1.44–2.36)]. Taken together with the current findings, this suggests that 15q14 plays a role in both common and high myopia.</p><p>The 15q14 associated region contains two interesting genes that are both well expressed in the retina, <italic>GJD2</italic> and <italic>ACTC1. GJD2</italic> encodes the Connexin36 protein, which plays a crucial role in the transmission and processing of visual signals in the retina by enabling intercellular transport of small molecules and ions in photoreceptors, amacrine and bipolar cells (Deans et al. <xref ref-type="bibr" rid="CR3">2002</xref>; Guldenagel et al. <xref ref-type="bibr" rid="CR8">2001</xref>; Kihara et al. <xref ref-type="bibr" rid="CR16">2009</xref>; Striedinger et al. <xref ref-type="bibr" rid="CR32">2005</xref>). We speculated that the protein encoded by the other candidate gene, <italic>ACTC1</italic>, could play a role in scleral remodeling, given the fact that similar actin proteins have been shown to be increased in developing myopic tree shrew eyes (Jobling et al. <xref ref-type="bibr" rid="CR13">2009</xref>). Previous <italic>GJD2</italic> (Solouki et al. <xref ref-type="bibr" rid="CR31">2010</xref>) and <italic>ACTC1</italic> (unpublished data) direct sequencing experiments did not reveal a functional variant, but the 15q14 locus appeared to harbor regulatory elements which may influence transcription of these genes (Solouki et al. <xref ref-type="bibr" rid="CR31">2010</xref>).</p><p>The 15q25 region contains the interesting candidate gene <italic>RASGRF1</italic>, which is highly expressed in the retina and has previously been implicated in photoreception and visual sensory processes (Fernandez-Medarde et al. <xref ref-type="bibr" rid="CR6">2009</xref>; Jones and Moses <xref ref-type="bibr" rid="CR14">2004</xref>). The association with this locus and gene is not robust, since none of the initial SNPs replicated significantly, and determination of more SNPs did not increase significance. A type 1 error may explain the initial finding. Another potential cause for the non-replication is a large variation in allele frequencies. The range of allele frequencies at 15q25 (0.28–0.63) was only slightly larger than at 15q14 (0.38–0.64) in our consortium, making this an unlikely explanation (Supplementary Figure 1). Finally, population stratification within cohorts did not appear to play a major role, since only two cohorts had significant principal components, which were addressed in the analyses.</p><p>Other GWAS loci were only found for high myopia in Asian case control studies, and they were located on chromosomes 11q24.1 (Nakanishi et al. <xref ref-type="bibr" rid="CR24">2009</xref>), 5p15 (Li et al. <xref ref-type="bibr" rid="CR17">2011a</xref>), 4q25 (Li et al. <xref ref-type="bibr" rid="CR18">2011b</xref>), and 13q12.12 (Shi et al. <xref ref-type="bibr" rid="CR30">2011</xref>). The locus on chromosome 5p15 harbors the excellent candidate gene <italic>CTNND2</italic> which is involved in retinal morphogenesis, adhesion, retinal cell architecture integrity (Duparc et al. <xref ref-type="bibr" rid="CR5">2006</xref>; Paffenholz et al. <xref ref-type="bibr" rid="CR25">1999</xref>), and was replicated in subjects of the same ethnicity (Lu et al. <xref ref-type="bibr" rid="CR20">2011</xref>). Replication studies for the 4q25 (Gao et al. <xref ref-type="bibr" rid="CR7">2012</xref>) and 11q24.1 (Wang et al. <xref ref-type="bibr" rid="CR35">2011</xref>) loci were only successful in case of the 4q25 locus; these loci did not have prominent candidate genes.</p><p>What should be the next steps? For 15q14, comprehensive resequencing of the entire associated region and the flanking genes can reveal the responsible gene defects which determine the association. Novel techniques such as next-generation sequencing are promising in this regard. Functional studies in knockout animals will shed light on potential protein effects. Finally, evaluation of gene-environment interactions may explain phenotypic variation and help identify high risk groups. For myopia genetics in general, performance of a genome-wide meta-analysis is a logical next step. The current CREAM collaboration is an excellent platform for this project.</p><p>In summary, we have convincingly demonstrated that common variants at chromosome 15q14 influence susceptibility for myopia in both Caucasian and Asian populations around the world. Identification of functional variants and responsible genes that explain this association will provide more insight in the complex etiology of myopia.</p></sec><sec id="Sec6" sec-type="materials|methods"><title>Materials and methods</title><sec id="Sec7"><title>Subjects and phenotyping</title><p>A total of 31 study cohorts from the Consortium of Refractive Error and Myopia (CREAM) participated in this meta-analysis. 29 population-based as well as 2 case–control studies were included. General methods, descriptives and phenotyping and genotyping methods of the study cohorts can be found in Table 1, the Supplementary Material and Supplementary Table 1, respectively. In short, 22 cohorts consisted of Caucasian, and 5 of Asian study subjects. All studies were performed with the approval of their local Medical Ethics Committee, and written informed consent was obtained from all participants in accordance with the Declaration of Helsinki.</p><p>All studies used a similar protocol for phenotyping. Exclusion criteria were age ≤10 years, and bilateral cataract surgery, laser refractive procedures or other intra-ocular procedures which might alter refraction. Eligible participants underwent a complete ophthalmologic examination including a non-dilated measurement of refractive error (Table <xref rid="Tab1" ref-type="table">1</xref>) of both eyes. Spherical equivalent was calculated according to the standard formula (SE = sphere + ½ cylinder), and the mean of two eyes was used for analysis. When data from only one eye were available, the SE of this eye was used. SE was categorized into low (SE from −1.5 to −3 D), moderate (SE from −3 to −6 D) and high (SE of −6 D or lower) myopia; and also into low (SE from +1.5 to +3 D), moderate (SE from +3 to +6 D) and high (SE of +6 D or higher) hyperopia. Emmetropia was defined as SE equal to or between −1.5 and +1.5 D.</p></sec><sec id="Sec8"><title>Genotyping and imputation</title><p>DNA was extracted according to standard procedures, and genotyping and imputation of SNPs across the entire genome was performed using various methods (Table <xref rid="Tab1" ref-type="table">1</xref>). Samples with a low call rate, with excess autosomal heterozygosity, with sex-mismatch, or outliers identified by the identity-by-state clustering analysis were excluded.</p></sec><sec id="Sec9"><title>Statistical analysis</title><sec id="Sec10"><title>Meta-analysis of allelic effects on spherical equivalent</title><p>We selected 19 SNPs within loci 15q14 (14 SNPs) and 15q25 (5 SNPs) with a <italic>P</italic> value of <10<sup>−6</sup> from two previous GWAS (Hysi et al. <xref ref-type="bibr" rid="CR11">2010</xref>; Solouki et al. <xref ref-type="bibr" rid="CR31">2010</xref>). Linear regression models with a 1 degree of freedom trend test were used to examine associations with SE as a quantitative trait outcome, adjusting for age and gender and significant principal components if applicable. From all population-based cohorts, we obtained effect allele, non effect allele, regression coefficient beta, standard error, <italic>P</italic> value, minor allele and minor allele frequency for each of these SNPs. METAL for Linux was used to perform a meta-analysis on betas and standard errors for all SNPs. First, discovery cohorts (Hysi et al. <xref ref-type="bibr" rid="CR11">2010</xref>; Solouki et al. <xref ref-type="bibr" rid="CR31">2010</xref>) and replication studies were analyzed separately, followed by a combined meta-analysis. As a second analysis, 26 additional SNPs within the same linkage disequilibrium (LD) block were selected and tested for association using the procedures mentioned above. For these analyses, Bonferroni corrected <italic>P</italic> values (0.05/number of tested SNPs) of 3.57 × 10<sup>−3</sup> for 15q14, and 1.0 × 10<sup>−2</sup> (5 SNPs, Table <xref rid="Tab2" ref-type="table">2</xref>) or 1.92 × 10<sup>−3</sup> (26 SNPs, Table 3 Supplementary Material) for 15q25 were considered statistically significant.</p></sec><sec id="Sec11"><title>Meta-analysis of risk of myopia for top SNP</title><p>From all population-based and case control studies, we obtained genotype distributions of the replicated top SNPs. We calculated heterogeneity (χ<sup>2</sup>, <italic>I</italic><sup>2</sup> calculated and corresponding <italic>P</italic> values) between studies, crude OR with corresponding 95 % CI and <italic>P</italic> value of moderate and high myopia versus moderate and high hyperopia with a random as well as fixed effects meta-analysis using Stata 11. When these analyses provided similar outcomes, data from fixed effect analysis were used. For studies without subjects with high or moderate hyperopia, emmetropia was used as a reference group. A standard <italic>P</italic> value of <0.05 was considered statistically significant.</p></sec></sec></sec><sec sec-type="supplementary-material" id="AppESM1"><title>Electronic supplementary material</title><sec id="SecESM1"><p><supplementary-material content-type="local-data" id="MOESM1"><media xlink:href="439_2012_1176_MOESM1_ESM.docx" mimetype="application" mime-subtype="msword"><caption><p>Supplementary material 1 (DOCX 155 kb)</p></caption></media></supplementary-material></p></sec></sec></body><back><ack><p>We gratefully thank the invaluable contributions of all study participants, their relatives and staff at the recruitment centers. We would like to acknowledge the following agencies and persons:</p><p><italic>1958 British Birth Cohort</italic> was funded by the Medical Research Council’s Health of the Public grant (PIs Power and Strachan); the Wellcome Trust (083478 to J.S.R.); the National Institute for Health Research as Specialist Biomedical Research Centres partnering respectively with Great Ormond Street and Moorfields Hospitals; and theUlverscroft Vision Research Group.</p><p><italic>AGES</italic> has been funded by National Institutes of Health (N01AG12100), the National Insitute on Aging and National Eye Institute Intramural Research Programs (ZIAAG007380, ZIAEY000401), Hjartavernd (the Icelandic Heart Association); and the Althingi (the Icelandic Parliament). This study acknowledges the contribution of collaborators on the vision component, Tamara Harris, Lenore Launer, Melissa Garcia, Susan Corwin, Fridbert Jonasson, Johanna Eyrun Sverrisdottir, Sigurdur Sigurdsson, and the staff at Hjartavernd.</p><p>Core support for <italic>ALSPAC</italic> was provided by the UK Medical Research Council (4882); the Wellcome Trust (076467); the University of Bristol; and for this research specifically by the National Eye Research Centre, Bristol (SCIAD053). The study acknowledges Cathy Williams as a guarantor for the contents of this paper.</p><p><italic>The AREDS</italic> studies were supported by contracts from National Eye Institute/National Institutes of Health, Bethesda, MD, with additional support from Bausch & Lomb Inc, Rochester, NY. The genotyping costs were supported by the National Eye Institute (R01 EY020483 to D.S.) and some of the analyses were supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, USA. AREDS acknowledges Emily Chew and Frederick Ferris, National Eye Institute, National Institutes of Health, Bethesda, MD; and the Center for Inherited Disease Research, Baltimore, MD where SNP genotyping was carried out.</p><p><italic>KORA</italic> would like to acknowledge Christian Geiger and the Center for Inherited Disease Research, Baltimore, MD where SNP genotyping was carried out.</p><p><italic>Australian Twins</italic> was supported by an Australian National Health and Medical Research Council (NHMRC) Enabling Grant (2004-2009, 350415, 2005-2007); Clifford Craig Medical Research Trust; Ophthalmic Research Institute of Australia; American Health Assistance Foundation; Peggy and Leslie Cranbourne Foundation; Foundation for Children; Jack Brockhoff Foundation; National Institutes of Health/National Eye Institute (RO1EY01824601 (2007-2010)); Pfizer Australia Senior Research Fellowship (to D.A.M.); and Australian NHMRC Career Development Award (to S.M.). Genotyping was funded by an NHMRC Medical Genomics Grant and NIH Center for Inherited Disease Research as part of an National Eye Institute National Institutes of Health project grant, Australian sample imputation analyses were carried out on the Genetic Cluster Computer which is financially supported by the Netherlands Scientific Organization (NWO48005003). Australian Twins thanks Stuart Macgregor, Grant W. Montgomery, Nicholas G. Martin, Scott D. Gordon, Dale R. Nyholt, Sarah E. Medland, Brian P. McEvoy, Margaret J. Wright, Anjali K. Henders, Megan J. Campbell for ascertaining and processing genotyping data; Jane MacKinnon, Shayne Brown, Lisa Kearns, Jonathan Ruddle, Paul Sanfilippo, Sandra Staffieri, Olivia Bigault, Colleen Wilkinson, Jamie Craig, Yaling Ma, Julie Barbour for assisting with clinical examinations; and Dr Camilla Day and staff.</p><p>The Blue Mountains Eye Study was supported by the Australian National Health & Medical Research Council (NH&MRC), Canberra Australia (974159, 211069, 457349, 512423, 475604, 529912); the Centre for Clinical Research Excellence in Translational Clinical Research in Eye Diseases; NH&MRC research fellowships (358702, 632909 to J.J.W, 1028444 to P.N.B.); and the Wellcome Trust, UK as part of Wellcome Trust Case Control Consortium 2 (A Viswanathan, P McGuffin, P Mitchell, F Topouzis, P Foster) for genotyping costs of the entire BMES population (085475B08Z, 08547508Z, 076113). The Centre for Eye Research Australia receives Operational Infrastructure Support from the Victorian government. BMES acknowledges Elena Rochtchina from the Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute University of Sydney (NSW Australia); John Attia, Rodney Scott, Elizabeth G. Holliday from the University of Newcastle (Newcastle, NSW Australia); Jing Xie, Maria Schache and Andrea J. Richardson from the Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne; Michael Inouye, The Walter and Elisa Hall Institute of Medical Research (Victoria, Australia); Ananth Viswanathan, Moorfields Eye Hospital (London, UK); Paul J. Foster, NIHR Biomedical Research Centre for Ophthalmology, UCL Institute of Ophthalmology & Moorfields Eye Hospital (London); Peter McGuffin, MRC Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King’s College (London, United Kingdom); Fotis Topouzis, Department of Ophthalmology, School of Medicine, Aristotle University of Thessaloniki, AHEPA Hospital (Thessaloniki, Greece); Xueling Sim, National University of Singapore; members of the Wellcome Trust Case Control Consortium 2. (Membership of Wellcome Trust Case Control Consortium 2 Peter Donnelly<sup>1,2</sup>, Ines Barroso<sup>3</sup>, Jenefer M Blackwell<sup>4, 5</sup>, Elvira Bramon<sup>6</sup>, Matthew A Brown<sup>7</sup>, Juan P Casas<sup>8</sup>, Aiden Corvin<sup>9</sup>, Panos Deloukas<sup>3</sup>, Audrey Duncanson<sup>10</sup>, Janusz Jankowski<sup>11</sup>, Hugh S Markus<sup>12</sup>, Christopher G Mathew<sup>13</sup>, Colin NA Palmer<sup>14</sup>, Robert Plomin<sup>15</sup>, Anna Rautanen<sup>1</sup>, Stephen J Sawcer<sup>16</sup>, Richard C Trembath<sup>13</sup>, Ananth C Viswanathan<sup>17</sup>, Nicholas W Wood<sup>18</sup>, Chris C A Spencer<sup>1</sup>, Gavin Band<sup>1</sup>, Céline Bellenguez<sup>1</sup>, Colin Freeman<sup>1</sup>, Garrett Hellenthal<sup>1</sup>, Eleni Giannoulatou<sup>1</sup>, Matti Pirinen<sup>1</sup>, Richard Pearson<sup>1</sup>, Amy Strange<sup>1</sup>, Zhan Su<sup>1</sup>, Damjan Vukcevic<sup>1</sup>, Cordelia Langford<sup>3</sup>, Sarah E Hunt<sup>3</sup>, Sarah Edkins<sup>3</sup>, Rhian Gwilliam<sup>3</sup>, Hannah Blackburn<sup>3</sup>, Suzannah J Bumpstead<sup>3</sup>, Serge Dronov<sup>3</sup>, Matthew Gillman<sup>3</sup>, Emma Gray<sup>3</sup>, Naomi Hammond<sup>3</sup>, Alagurevathi Jayakumar<sup>3</sup>, Owen T McCann<sup>3</sup>, Jennifer Liddle<sup>3</sup>, Simon C Potter<sup>3</sup>, Radhi Ravindrarajah<sup>3</sup>, Michelle Ricketts<sup>3</sup>, Matthew Waller<sup>3</sup>, Paul Weston<sup>3</sup>, Sara Widaa<sup>3</sup>, Pamela Whittaker<sup>3</sup> 1 Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7LJ, UK; 2 Dept Statistics, University of Oxford, Oxford OX1 3TG, UK; 3 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK; 4 Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, 100 Roberts Road, Subiaco, Western Australia 6008; 5 Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge CB2 0XY, UK; 6 Department of Psychosis Studies, NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King’s College London and The South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AF, UK; 7 University of Queensland Diamantina Institute, Brisbane, Queensland, Australia; 8 Dept Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT and Dept Epidemiology and Public Health, University College London WC1E 6BT, UK; 9 Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Eire; 10 Molecular and Physiological Sciences, The Wellcome Trust, London NW1 2BE; 11 Centre for Digestive Diseases, Queen Mary University of London, London E1 2AD, UK and Digestive Diseases Centre, Leicester Royal Infirmary, Leicester LE7 7HH, UK and Department of Clinical Pharmacology, Old Road Campus, University of Oxford, Oxford OX3 7DQ, UK; 12 Clinical Neurosciences, St George’s University of London, London SW17 0RE; 13 King’s College London Dept Medical and Molecular Genetics, School of Medicine, Guy’s Hospital, London SE1 9RT, UK; 14 Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK; 15 King’s College London Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Denmark Hill, London SE5 8AF, UK; 16 University of Cambridge Dept Clinical Neurosciences, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK; 17
NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1 V 2PD, UK; 18 Dept Molecular Neuroscience, Institute of Neurology, Queen Square, London WC1 N 3BG, UK.).</p><p><italic>The CROATIA studies</italic> were funded by grants from the Medical Research Council (UK) and from the Republic of Croatia Ministry of Science, Education and Sports (10810803150302); and the CROATIA-Korcula genotyping was funded by the European Union framework program 6 project EUROSPAN (LSHGCT2006018947). The CROATIA studies acknowledges Dr. Goran Bencic, Prof. Zoran Vatavuk, Biljana Andrijević Derk, Valentina Lacmanović Lončar, Krešimir Mandić, Antonija Mandić, Ivan Škegro, Jasna Pavičić Astaloš, Ivana Merc, Miljenka Martinović, Petra Kralj, Tamara Knežević and Katja Barać-Juretić as well as the recruitment team from the Croatian Centre for Global Health, University of Split and the Institute of Anthropological Research in Zagreb for the ophthalmological data collection; Peter Lichner and the Helmholtz Zentrum Munchen (Munich, Germany), AROS Applied Biotechnology, Aarhus, Denmark and the Wellcome Trust Clinical facility (Edinburgh, United Kingdom) for the SNP genotyping all studies.</p><p><italic>ORCADES</italic> was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, the Medical Research Council Human Genetics Unit and the European Union framework program 6 EUROSPAN project (LSHGCT2006018947). ORCADES acknowledges the invaluable contributions of Lorraine Anderson and the research nurses in Orkney, in particular Margaret Pratt who performed the eye measurements,as well as the administrative team in Edinburgh University; and the Wellcome Trust Clinical facility (Edinburgh, United Kingdom) for DNA extraction; and Peter Lichner and the Helmholtz Zentrum Munchen (Munich, Germany) for genotyping.</p><p><italic>EGCUT</italic> received financing by FP7 grants (201413, 245536); Estonian Government (SF0180142s08); and the European Union through the European Regional Development Fund, in the frame of Centre of Excellence in Genomics and Estonian Research Infrastructure’s Roadmap. EGCUT acknowledges Ms. M. Hass and Mr. V. Soo.</p><p><italic>FITSA</italic> was supported by ENGAGE (FP7-HEALTH-F4-2007, 201413); the Academy of Finland Center of Excellence in Complex Disease Genetics (213506, 129680); the Academy of Finland Ageing Programme; and the Finnish Ministry of Culture and Education and University of Jyväskylä. For FITSA the contributions of Emmi Tikkanen, Samuli Ripatti and Jaakko Kaprio are acknowledged.</p><p><italic>Framingham Eye Study</italic> was supported by NEI (N01EY22112, N01EY92109); the National Heart, Lung, and Blood Institute (N02HL64278) for SHARe genotyping; Boston University (N01HC25195); and by intramural funds of the National Human Genome Research Institute, NIH, USA (to R.W. and J.E.B.W.) <italic>GHS</italic> was funded through the government of Rheinland-Pfalz (“Stiftung Rheinland Pfalz für Innovation” (AZ961386261733); the research programs “Wissen schafft Zukunft” and “Schwerpunkt Vaskuläre Prävention” of the Johannes Gutenberg-University of Mainz; Boehringer Ingelheim; PHILIPS Medical Systems; National Genome Network “NGFNplus” by the Federal Ministry of Education and Research, Germany (A301GS0833).</p><p><italic>KORA</italic> was financed by the Helmholtz Center Munich, German Research Center for Environmental Health; the German Federal Ministry of Education and Research; the State of Bavaria; the German National Genome Research Network (NGFN-2 and NGFNPlus) (01GS0823); Munich Center of Health Sciences as part of LMUinnovativ; the German Research Counsil (DFG) (WI182041 to K.O.); the genotyping costs were supported by the National Eye Institute (R01 EY020483 to D.S.) and some of the analyses were supported by the Intramural Research Program of the National Human Genome.</p><p><italic>The Kyoto Study</italic> was supported by the Japan Society for the Promotion of Science, Tokyo (21249084, 22791653).</p><p><italic>MESA</italic> and MESA SNP Health Association Resource (SHARe) are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) (N01HC95159, N01HC95169, RR-024156, N02HL64278 (SHARe genotyping)); the National Institutes of Health (Intramural Research Program of the National Eye Institute, (ZIAEY000403); (R01HL071205 to MESA Family); the Clinical Translational Science Institute (UL1RR033176); and the Cedars-Sinai General Clinical Research Center (RR00425). MESA thanks all investigators, especially Drs. Mary Frances Cotch, Jerome I. Rotter, Ronald Klein, and Tien Y. Wong in the Eye Working Group, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at <ext-link ext-link-type="uri" xlink:href="http://www.mesa-nhlbi.org">http://www.mesa-nhlbi.org</ext-link>.</p><p><italic>OGP Talana</italic> was supported by grants from the Italian Ministry of Education, University and Research (5571DSPAR2002, 718Ric2005). OGP Talana thanks the Ogliastra population and the municipal administrators for their collaboration to the project and for economic and logistic support.</p><p><italic>The Rotterdam Study and ERF</italic> were supported by the Netherlands Organisation of Scientific Research (NWO) (Vidi 91796357); Erasmus Medical Center and Erasmus University, Rotterdam, The Netherlands; Netherlands Organization for Health Research and Development (ZonMw); UitZicht; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission (DG XII); the Municipality of Rotterdam; the Netherlands Genomics Initiative/NWO; Center for Medical Systems Biology of NGI; Lijf en Leven; M.D. Fonds; Henkes Stichting; Stichting Nederlands Oogheelkundig Onderzoek; Swart van Essen; Bevordering van Volkskracht; Blindenhulp; Landelijke Stichting voor Blinden en Slechtzienden; Rotterdamse Vereniging voor Blindenbelangen; OOG; Algemene Nederlandse Vereniging ter Voorkoming van Blindheid; the Rotterdam Eye Hospital Research Foundation; and Topcon Europe. Rotterdam Study and ERF thank Ada Hooghart, Corina Brussee, Riet Bernaerts-Biskop, Patricia van Hilten, Pascal Arp, Jeanette Vergeer, Marijn Verkerk and Sander Bervoets<bold>.</bold></p><p><italic>The Singapore studies (SCORM, SP2, SiMES, SINDI)</italic> were supported by the National Medical Research Council, Singapore (NMRC 07962003, NMRC 11762008), Singapore Bio-Medical Research Council (0612119466, 0913519616).</p><p><italic>The Sorbs study</italic> was supported by the Interdisciplinary Centre for Clinical Research at the University of Leipzig (B27 to A.T.) from the German Diabetes Association (to A.T.); the DHFD, Diabetes Hilfs- und Forschungsfonds Deutschland (to A.T.); the European Commission under a Marie Curie Intra-European Fellowship (to R.M.); the European Community's Seventh Framework Programme (FP720072013); and ENGAGE project (HEALTHF42007201413). We thank Michael Stumvoll and Peter Kovacs for the excellent project coordination and fruitful discussion, furthermore Knut Krohn (Microarray Core Facility of the Interdisciplinary Centre for Clinical Research, University of Leipzig) for the genotyping support.</p><p><italic>TwinsUK</italic> received funding from the Wellcome Trust; the European Union MyEuropia Marie Curie Research Training Network; Guide Dogs for the Blind Association; the European Community’s FP7 (HEALTHF22008201865GEFOS); ENGAGE (HEALTHF42007201413); the FP-5 GenomEUtwin Project (QLG2CT200201254); US National Institutes of Health/National Eye Institute (1RO1EY018246); NIH Center for Inherited Disease Research; the National Institute for Health Research comprehensive Biomedical Research Centre award to Guy’s and St. Thomas’ National Health Service Foundation Trust partnering with King’s College London.</p><p><italic>The Young Finns Study</italic> was financially supported by the Academy of Finland (134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi)); the Social Insurance Institution of Finland, Kuopio, Tampere; Turku University Hospital Medical Funds (grant 9M048 to T.L.); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation of Cardiovascular Research and Finnish Cultural Foundation; Tampere Tuberculosis Foundation; and Emil Aaltonen Foundation (to T.L.).</p><sec id="d29e4867"><title>Conflict of interest</title><p>The authors declare that they have no conflict of interest.</p></sec><sec id="d29e4872"><title>Ethical standards</title><p>The experiments comply with the current laws in which they were performed.</p></sec><sec id="d29e4877"><title>Open Access</title><p>This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.</p></sec></ack><ref-list id="Bib1"><title>References</title><ref 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| This area was generated with Dilib version V0.6.33. |  |