Seven new loci associated with age-related macular degeneration

Journal name:
Nature Genetics
Volume:
45,
Pages:
433–439
Year published:
DOI:
doi:10.1038/ng.2578
Received
Accepted
Published online

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P < 5 × 10−8. These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P < 5 × 10−8 for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.

At a glance

Figures

  1. Summary of GWAS results.
    Figure 1: Summary of GWAS results.

    Summary of genome-wide association results in the discovery GWAS sample. Previously described loci with associations reaching P < 5 × 10−8 are labeled in blue; new loci with associations reaching P < 5 × 10−8 for the first time after follow-up analysis are labeled in green. The dashed horizontal lines represent thresholds for follow-up (P < 1 × 10−5, orange) and genome-wide significance (P < 5 × 10−6, red) as well as a discontinuity in the y axis (at P < 1 × 10−16, gray).

  2. Sensitivity analysis.
    Figure 2: Sensitivity analysis.

    Top left, estimated effect sizes for the original analysis are compared to those for an age-adjusted analysis (where age was included as a covariate and samples of unknown age were excluded). Top right, comparison of analyses stratified by sex. Bottom left, comparison of analyses stratified by disease subtype. GA, geographic atrophy; NV, neovascularization. Bottom right, comparison of disease stratified by ancestry. The size of each marker reflects confidence intervals (with height reflecting the confidence interval along the y axis and width reflecting the confidence interval along the x axis). Comparisons reaching P < 0.05 are labeled and colored in red.

  3. Risk score analysis.
    Figure 3: Risk score analysis.

    We calculated a risk score for each individual, defined as the product of the number of risk alleles at each locus and the associated effect size for each allele (measured on the log-odds scale). The plot summarizes the ability of these overall genetic risk scores to distinguish cases and controls. Analyses were carried out using the 19 SNPs that reached P < 5 × 10−8 here, the 12 SNPs previously reaching this threshold and the 7 new variants.

Accession codes

Referenced accessions

Gene Expression Omnibus

NCBI Reference Sequence

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Author information

  1. These authors contributed equally to this work.

    • Lars G Fritsche,
    • Wei Chen,
    • Matthew Schu,
    • Brian L Yaspan &
    • Yi Yu
  2. These authors jointly directed this work.

    • Rando Allikmets,
    • Paul N Baird,
    • Michael B Gorin,
    • Jie Jin Wang,
    • Caroline C W Klaver,
    • Johanna M Seddon,
    • Margaret A Pericak-Vance,
    • Sudha K Iyengar,
    • John R W Yates,
    • Anand Swaroop,
    • Bernhard H F Weber,
    • Michiaki Kubo,
    • Margaret M DeAngelis,
    • Thierry Léveillard,
    • Unnur Thorsteinsdottir,
    • Jonathan L Haines,
    • Lindsay A Farrer,
    • Iris M Heid &
    • Gonçalo R Abecasis

Affiliations

  1. Institute of Human Genetics, University of Regensburg, Regensburg, Germany.

    • Lars G Fritsche &
    • Bernhard H F Weber
  2. Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.

    • Lars G Fritsche,
    • Wei Chen,
    • Xueling Sim &
    • Gonçalo R Abecasis
  3. Division of Pediatric Pulmonary Medicine, Allergy and Immunology, Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

    • Wei Chen
  4. Section of Biomedical Genetics, Department of Medicine, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA.

    • Matthew Schu,
    • Gyungah Jun &
    • Lindsay A Farrer
  5. Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

    • Brian L Yaspan &
    • Jonathan L Haines
  6. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Brian L Yaspan &
    • Jonathan L Haines
  7. Ophthalmic Epidemiology and Genetics Service, Tufts Medical Center, Boston, Massachusetts, USA.

    • Yi Yu,
    • Kimberly A Chin,
    • Robyn Reynolds &
    • Johanna M Seddon
  8. deCODE Genetics, Reykjavik, Iceland.

    • Gudmar Thorleifsson,
    • Hreinn Stefansson,
    • Kari Stefansson &
    • Unnur Thorsteinsdottir
  9. Department of Molecular Biology and Genetics, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Donald J Zack
  10. Department of Genetics, Institut de la Vision, Université Pierre et Marie Curie–Université Paris 6, Unité Mixte de Recherche Scientifique (UMRS) 968, Paris, France.

    • Donald J Zack,
    • Isabelle Audo,
    • José-Alain Sahel &
    • Thierry Léveillard
  11. Department of Neuroscience, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Donald J Zack &
    • Peter A Campochiaro
  12. Institute of Genetic Medicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Donald J Zack
  13. Laboratory for Genotyping Development, Research Group for Genotyping, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan.

    • Satoshi Arakawa &
    • Michiaki Kubo
  14. Moorfields Eye Hospital, London, UK.

    • Valentina Cipriani,
    • Alan C Bird,
    • Anthony T Moore,
    • Andrew R Webster &
    • John R W Yates
  15. Institute of Ophthalmology, University College London, London, UK.

    • Valentina Cipriani,
    • Isabelle Audo,
    • Alan C Bird,
    • Anthony T Moore,
    • José-Alain Sahel,
    • Andrew R Webster &
    • John R W Yates
  16. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Stephan Ripke &
    • Mark J Daly
  17. Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.

    • Stephan Ripke
  18. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.

    • Robert P Igo Jr,
    • Peronne Joseph,
    • Barbara J Truitt &
    • Sudha K Iyengar
  19. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Gabriëlle H S Buitendijk,
    • André G Uitterlinden,
    • Cornelia M van Duijn,
    • Johannes R Vingerling &
    • Caroline C W Klaver
  20. Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Gabriëlle H S Buitendijk,
    • Johannes R Vingerling &
    • Caroline C W Klaver
  21. Centre for Molecular Epidemiology, National University of Singapore, Singapore.

    • Xueling Sim
  22. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Daniel E Weeks
  23. Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Daniel E Weeks
  24. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.

    • Robyn H Guymer,
    • Melinda S Cain,
    • Andrea J Richardson,
    • Tien Y Wong,
    • Paul N Baird &
    • Jie Jin Wang
  25. Department of Ophthalmology, Columbia University, New York, New York, USA.

    • Joanna E Merriam,
    • Gaetano R Barile,
    • R Theodore Smith &
    • Rando Allikmets
  26. Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.

    • Peter J Francis &
    • Michael L Klein
  27. Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.

    • Gregory Hannum
  28. Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

    • Anita Agarwal
  29. Department of Ophthalmology & Visual Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Anita Agarwal
  30. Department of Ophthalmology, University of Edinburgh and Princess Alexandra Eye Pavilion, Edinburgh, UK.

    • Ana Maria Armbrecht,
    • Baljean Dhillon &
    • Saddek Mohand-Saïd
  31. Institut National de la Santé et de la Recherche Médicale (INSERM) U968, Paris, France.

    • Isabelle Audo,
    • José-Alain Sahel &
    • Thierry Léveillard
  32. Centre National de la Recherche Scientifique (CNRS), UMR 7210, Paris, France.

    • Isabelle Audo,
    • Saddek Mohand-Saïd,
    • José-Alain Sahel &
    • Thierry Léveillard
  33. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.

    • Tin Aung,
    • Ching-Yu Cheng,
    • Belinda K Cornes,
    • Eranga N Vithana &
    • Tien Y Wong
  34. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

    • Tin Aung,
    • Ching-Yu Cheng,
    • Eranga N Vithana &
    • Tien Y Wong
  35. Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM–Direction de l'Hospitalisation et de l'Organisation des Soins, Centres d'Investigation Clinique 503, Paris, France.

    • Mustapha Benchaboune,
    • Saddek Mohand-Saïd &
    • José-Alain Sahel
  36. Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.

    • Paul N Bishop
  37. Central Manchester University Hospitals National Health Service (NHS) Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

    • Paul N Bishop
  38. Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.

    • Kari E Branham,
    • John R Heckenlively,
    • Mohammad I Othman &
    • Anand Swaroop
  39. Neurobiology Neurodegeneration & Repair Laboratory (N-NRL), National Eye Institute, US National Institutes of Health, Bethesda, Maryland, USA.

    • Matthew Brooks,
    • Radu Cojocaru,
    • James S Friedman,
    • Neel Gupta,
    • Rinki Ratna Priya &
    • Anand Swaroop
  40. Scheie Eye Institute, Penn Presbyterian Medical Center, Philadelphia, Pennsylvania, USA.

    • Alexander J Brucker
  41. John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.

    • William H Cade,
    • Adam C Naj,
    • William K Scott &
    • Margaret A Pericak-Vance
  42. Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.

    • William H Cade,
    • Adam C Naj,
    • William K Scott &
    • Margaret A Pericak-Vance
  43. Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Peter A Campochiaro &
    • Hendrik P N Scholl
  44. Immunopathology Section, Laboratory of Immunology, National Eye Institute, US National Institutes of Health, Bethesda, Maryland, USA.

    • Chi-Chao Chan
  45. Saw Swee Hock School of Public Health, National University of Singapore, Singapore.

    • Ching-Yu Cheng
  46. Centre for Quantitative Medicine, Office of Clinical Sciences, Duke–National University of Singapore Graduate Medical School, Singapore.

    • Ching-Yu Cheng
  47. Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute, US National Institutes of Health, Bethesda, Maryland, USA.

    • Emily Y Chew
  48. Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

    • Itay Chowers
  49. Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.

    • David G Clayton,
    • Jane C Khan,
    • Humma Shahid &
    • John R W Yates
  50. Department of Health Promotion and Development, School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Yvette P Conley
  51. Institute for Molecular Biology, University of Oregon, Eugene, Oregon, USA.

    • Albert O Edwards
  52. Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.

    • Evangelos Evangelou
  53. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Jesen Fagerness
  54. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.

    • Jesen Fagerness
  55. Department of Ophthalmology, University of California, San Diego, La Jolla, California, USA.

    • Henry A Ferreyra,
    • Guy Hughes,
    • Igor Kozak,
    • Clara J Lee,
    • Ming Zhang,
    • Ling Zhao &
    • Kang Zhang
  56. Shiley Eye Center, University of California, San Diego, La Jolla, California, USA.

    • Henry A Ferreyra,
    • Guy Hughes,
    • Igor Kozak,
    • Clara J Lee,
    • Ming Zhang,
    • Ling Zhao &
    • Kang Zhang
  57. Department of Ophthalmology, National University Hospital, Reykjavik, Iceland.

    • Asbjorg Geirsdottir &
    • Haraldur Sigurdsson
  58. Glaucoma Project, Vision Research Foundation, Sankara Nethralaya, Chennai, India.

    • Ronnie J George &
    • Lingam Vijaya
  59. Institute of Genetic Epidemiology, Helmholtz Zentrum München–Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany.

    • Christian Gieger &
    • Iris M Heid
  60. Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

    • Stephanie A Hagstrom,
    • Gayle J T Pauer &
    • Neal S Peachey
  61. Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

    • Simon P Harding
  62. Augenklinik, Ludwig-Maximilians-Universität München, Munich, Germany.

    • Christos Haritoglou &
    • Guenther Rudolph
  63. Department of Ophthalmology, University of Bonn, Bonn, Germany.

    • Frank G Holz &
    • Hendrik P N Scholl
  64. Institute for Genomic Medicine, University of California, San Diego, La Jolla, California, USA.

    • Guy Hughes,
    • Clara J Lee,
    • Ming Zhang,
    • Ling Zhao &
    • Kang Zhang
  65. Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.

    • John P A Ioannidis
  66. Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA.

    • John P A Ioannidis
  67. Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, California, USA.

    • John P A Ioannidis
  68. Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.

    • Tatsuro Ishibashi
  69. Department of Ophthalmology, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA.

    • Gyungah Jun &
    • Lindsay A Farrer
  70. Department of Biostatistics, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA.

    • Gyungah Jun &
    • Lindsay A Farrer
  71. Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France.

    • Yoichiro Kamatani &
    • G Mark Lathrop
  72. Center for Human Disease Modeling, Duke University, Durham, North Carolina, USA.

    • Nicholas Katsanis
  73. Department of Cell Biology, Duke University, Durham, North Carolina, USA.

    • Nicholas Katsanis
  74. Department of Pediatrics, Duke University, Durham, North Carolina, USA.

    • Nicholas Katsanis
  75. Department of Ophthalmology, Julius-Maximilians-Universität, Würzburg, Germany.

    • Claudia N Keilhauer
  76. Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia, Australia.

    • Jane C Khan
  77. Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, Australia.

    • Jane C Khan
  78. Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.

    • Ivana K Kim,
    • Debra A Schaumberg &
    • Lucia Sobrin
  79. Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.

    • Ivana K Kim &
    • Lucia Sobrin
  80. Department of Environmental Medicine, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.

    • Yutaka Kiyohara
  81. Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.

    • Barbara E K Klein,
    • Ronald Klein,
    • Kristine E Lee &
    • Chelsea E Myers
  82. Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.

    • Jaclyn L Kovach &
    • Stephen G Schwartz
  83. Institute of Human Genetics, Helmholtz Zentrum München–Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany.

    • Peter Lichtner &
    • Thomas Meitinger
  84. Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton, UK.

    • Andrew J Lotery
  85. Institute of Human Genetics, Technische Universität München, Munich, Germany.

    • Thomas Meitinger
  86. Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia.

    • Paul Mitchell &
    • Jie Jin Wang
  87. Department of Therapeutics, Institut de la Vision, Université Pierre et Marie Curie–Université Paris 6, UMRS 968, Paris, France.

    • Saddek Mohand-Saïd
  88. Department of Ophthalmology and Visual Sciences, University of Utah, John A. Moran Eye Center, Salt Lake City, Utah, USA.

    • Denise J Morgan,
    • Margaux A Morrison &
    • Margaret M DeAngelis
  89. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

    • Yusuke Nakamura
  90. Laboratory for Statistical Analysis, CGM, RIKEN, Yokohama, Japan.

    • Yukinori Okada &
    • Atsushi Takahashi
  91. Department of Ophthalmology, Weill Cornell Medical College, New York, New York, USA.

    • Anton Orlin
  92. Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • M Carolina Ortube &
    • Michael B Gorin
  93. Jules Stein Eye Institute, Los Angeles, California, USA.

    • M Carolina Ortube &
    • Michael B Gorin
  94. Moran Center for Translational Medicine, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA.

    • Chris Pappas &
    • Gregory S Hageman
  95. Research Service, Louis Stokes Veteran Affairs Medical Center, Cleveland, Ohio, USA.

    • Kyu Hyung Park
  96. Laboratory of Integrative Bioinformatics and Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.

    • Neal S Peachey &
    • Gwen M Sturgill-Short
  97. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.

    • Olivier Poch &
    • Raymond Ripp
  98. Fondation Ophtalmologique Adolphe de Rothschild, Paris, France.

    • Euijung Ryu &
    • Nirubol Tosakulwong
  99. Académie des Sciences–Institut de France, Paris, France.

    • José-Alain Sahel
  100. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • José-Alain Sahel
  101. Department of Ophthalmology, Addenbrooke's Hospital, Cambridge, UK.

    • Debra A Schaumberg
  102. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Humma Shahid
  103. Centre for Vision and Vascular Science, Queen's University, Belfast, UK.

    • Haraldur Sigurdsson,
    • Kari Stefansson &
    • Unnur Thorsteinsdottir
  104. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

    • Giuliana Silvestri
  105. Department of Biomedical Engineering, Columbia University, New York, New York, USA.

    • Theru A Sivakumaran
  106. Centre de Recherche Clinique d'Ophthalmologie, Hôpital Intercommunal de Créteil, Hôpital Henri Mondor, Université Paris Est, Créteil, France.

    • R Theodore Smith
  107. Department of Ophthalmology and Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Eric H Souied
  108. Department of Ophthalmology, University of Thessaly School of Medicine, Larissa, Greece.

    • Dwight E Stambolian
  109. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Evangelia E Tsironi
  110. Institute of Epidemiology I, Helmholtz Zentrum München–Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany.

    • André G Uitterlinden
  111. Institute of Medical Informatics, Ludwig-Maximilians-Universität and Klinikum Großhadern, Munich, Germany.

    • H-Erich Wichmann
  112. Institute of Biometry, Ludwig-Maximilians-Universität and Klinikum Großhadern, Munich, Germany.

    • H-Erich Wichmann
  113. Institute of Epidemiology, Ludwig-Maximilians-Universität and Klinikum Großhadern, Munich, Germany.

    • H-Erich Wichmann
  114. Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.

    • H-Erich Wichmann
  115. Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, UK.

    • Thomas W Winkler &
    • Iris M Heid
  116. Centre National de Génotypage, Centre d'Energie Atomique–Institut de Génomique (IG), Evry, France.

    • Alan F Wright
  117. Molecular Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.

    • Diana Zelenika &
    • G Mark Lathrop
  118. Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.

    • Ming Zhang &
    • Kang Zhang
  119. Center for Translational Medicine, University of Utah, John A. Moran Eye Center, Salt Lake City, Utah, USA.

    • Ming Zhang &
    • Kang Zhang
  120. Department of Pathology & Cell Biology, Columbia University, New York, New York, USA.

    • Rando Allikmets
  121. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • Michael B Gorin
  122. Department of Ophthamology, Tufts University School of Medicine, Boston, Massachusetts, USA.

    • Johanna M Seddon
  123. Department of Genetics, Case Western Reserve University, Cleveland, Ohio, USA.

    • Sudha K Iyengar
  124. Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA.

    • Sudha K Iyengar
  125. Center for Clinical Investigation, Case Western Reserve University, Cleveland, Ohio, USA.

    • Sudha K Iyengar
  126. Department of Neurology, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA.

    • Lindsay A Farrer
  127. Department of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA.

    • Lindsay A Farrer

Consortia

  1. The AMD Gene Consortium

    • Lars G Fritsche,
    • Wei Chen,
    • Matthew Schu,
    • Brian L Yaspan,
    • Yi Yu,
    • Gudmar Thorleifsson,
    • Donald J Zack,
    • Satoshi Arakawa,
    • Valentina Cipriani,
    • Stephan Ripke,
    • Robert P Igo Jr,
    • Gabriëlle H S Buitendijk,
    • Xueling Sim,
    • Daniel E Weeks,
    • Robyn H Guymer,
    • Joanna E Merriam,
    • Peter J Francis,
    • Gregory Hannum,
    • Anita Agarwal,
    • Ana Maria Armbrecht,
    • Isabelle Audo,
    • Tin Aung,
    • Gaetano R Barile,
    • Mustapha Benchaboune,
    • Alan C Bird,
    • Paul N Bishop,
    • Kari E Branham,
    • Matthew Brooks,
    • Alexander J Brucker,
    • William H Cade,
    • Melinda S Cain,
    • Peter A Campochiaro,
    • Chi-Chao Chan,
    • Ching-Yu Cheng,
    • Emily Y Chew,
    • Kimberly A Chin,
    • Itay Chowers,
    • David G Clayton,
    • Radu Cojocaru,
    • Yvette P Conley,
    • Belinda K Cornes,
    • Mark J Daly,
    • Baljean Dhillon,
    • Albert O Edwards,
    • Evangelos Evangelou,
    • Jesen Fagerness,
    • Henry A Ferreyra,
    • James S Friedman,
    • Asbjorg Geirsdottir,
    • Ronnie J George,
    • Christian Gieger,
    • Neel Gupta,
    • Stephanie A Hagstrom,
    • Simon P Harding,
    • Christos Haritoglou,
    • John R Heckenlively,
    • Frank G Holz,
    • Guy Hughes,
    • John P A Ioannidis,
    • Tatsuro Ishibashi,
    • Peronne Joseph,
    • Gyungah Jun,
    • Yoichiro Kamatani,
    • Nicholas Katsanis,
    • Claudia N Keilhauer,
    • Jane C Khan,
    • Ivana K Kim,
    • Yutaka Kiyohara,
    • Barbara E K Klein,
    • Ronald Klein,
    • Jaclyn L Kovach,
    • Igor Kozak,
    • Clara J Lee,
    • Kristine E Lee,
    • Peter Lichtner,
    • Andrew J Lotery,
    • Thomas Meitinger,
    • Paul Mitchell,
    • Saddek Mohand-Saïd,
    • Anthony T Moore,
    • Denise J Morgan,
    • Margaux A Morrison,
    • Chelsea E Myers,
    • Adam C Naj,
    • Yusuke Nakamura,
    • Yukinori Okada,
    • Anton Orlin,
    • M Carolina Ortube,
    • Mohammad I Othman,
    • Chris Pappas,
    • Kyu Hyung Park,
    • Gayle J T Pauer,
    • Neal S Peachey,
    • Olivier Poch,
    • Rinki Ratna Priya,
    • Robyn Reynolds,
    • Andrea J Richardson,
    • Raymond Ripp,
    • Guenther Rudolph,
    • Euijung Ryu,
    • José-Alain Sahel,
    • Debra A Schaumberg,
    • Hendrik P N Scholl,
    • Stephen G Schwartz,
    • William K Scott,
    • Humma Shahid,
    • Haraldur Sigurdsson,
    • Giuliana Silvestri,
    • Theru A Sivakumaran,
    • R Theodore Smith,
    • Lucia Sobrin,
    • Eric H Souied,
    • Dwight E Stambolian,
    • Hreinn Stefansson,
    • Gwen M Sturgill-Short,
    • Atsushi Takahashi,
    • Nirubol Tosakulwong,
    • Barbara J Truitt,
    • Evangelia E Tsironi,
    • André G Uitterlinden,
    • Cornelia M van Duijn,
    • Lingam Vijaya,
    • Johannes R Vingerling,
    • Eranga N Vithana,
    • Andrew R Webster,
    • H-Erich Wichmann,
    • Thomas W Winkler,
    • Tien Y Wong,
    • Alan F Wright,
    • Diana Zelenika,
    • Ming Zhang,
    • Ling Zhao,
    • Kang Zhang,
    • Michael L Klein,
    • Gregory S Hageman,
    • G Mark Lathrop,
    • Kari Stefansson,
    • Rando Allikmets,
    • Paul N Baird,
    • Michael B Gorin,
    • Jie Jin Wang,
    • Caroline C W Klaver,
    • Johanna M Seddon,
    • Margaret A Pericak-Vance,
    • Sudha K Iyengar,
    • John R W Yates,
    • Anand Swaroop,
    • Bernhard H F Weber,
    • Michiaki Kubo,
    • Margaret M DeAngelis,
    • Thierry Léveillard,
    • Unnur Thorsteinsdottir,
    • Jonathan L Haines,
    • Lindsay A Farrer,
    • Iris M Heid &
    • Gonçalo R Abecasis

Contributions

AMD Gene Analysis Committee: L.G.F., W.C., M.S., B.L.Y., Y.Y., L.A.F., I.M.H. (co-lead) and G.R.A. (co-lead). AMD Gene Phenotype Committee: R.K., C.C.W.K., T.L., J.M.S. (lead) and J.J.W. (co-lead). AMD Gene Steering Committee: B.H.F.W. (chair, senior executive committee), G.R.A. (senior executive committee), M.M.D. (senior executive committee), J.L.H. (senior executive committee), S.K.I. (senior executive committee), M.A.P.-V. (senior executive committee), R.A., P.N. Baird, C.C.W.K., B.E.K.K., M.L.K., M.K., T.L., J.M.S., U.T., D.E.W., J.R.W.Y. and K.Z. AMD-EU-JHU: D.J.Z., I.A., M. Benchaboune, A.C.B., P.A.C., I.C., F.G.H., Y. Kamatani, N.K., A.J.L., S.M.-S., O.P., R. Ripp, J.-A.S., H.P.N.S., E.H.S., A.R.W., D.Z., G.M.L. and T.L. contributed phenotypes, genotypes and analyses for the AMD-EU-JHU study. BDES: R.P.I., B.E.K.K., R.K., K.E.L., C.E.M., T.A.S., B.J.T. and S.K.I. contributed phenotypes, genotypes and analyses for the BDES study. Blue Mountains Eye Study: X.S., P.M., T.Y.W. and J.J.W. contributed phenotypes, genotypes and analyses for BMES. BU/Utah: M.S., G.S.H., G.J., I.K.K., D.J.M., M.A.M., C.P., K.H.P., D.A.S., G.S., E.E.T., M.M.D. and L.A.F. contributed phenotypes, genotypes and analyses for the BU/Utah study. CCF/VAMC: S.A.H., P.J., G.J.T.P., N.S.P., G.M.S.-S., R.P.I. and S.K.I. contributed phenotypes, genotypes and analyses for the CCF/VAMC study. CEI: P.J.F. and M.L.K. contributed phenotypes, genotypes and analyses for the CEI study. Columbia: J.E.M., G.R.B., R.T.S. and R.A. contributed phenotypes, genotypes and analyses for the Columbia study. deCODE: A.G., G.T., H. Sigurdsson, H. Stefansson, K.S. and U.T. contributed phenotypes, genotypes and analyses for the deCODE study. Japan Age-Related Eye Diseases Study: S.A., T.I., Y. Kiyohara, Y.N., Y.O., A.T. and M.K. contributed phenotypes, genotypes and analyses for JAREDS. Melbourne: R.H.G., M.S.C., A.J.R. and P.N. Baird contributed phenotypes, genotypes and analyses for the Melbourne study. Miami/Vanderbilt: B.L.Y., A.A., W.H.C., J.L.K., A.C.N., S.G.S., W.K.S., M.A.P.-V. and J.L.H. contributed phenotypes, genotypes and analyses for the Miami/Vanderbilt study. MMAP/NEI: W.C., K.E.B., M. Brooks, A.J.B., C.-C.C., E.Y.C., R.C., A.O.E., J.S.F., N.G., J.R.H., A.O., M.I.O., R.R.P., E.R., D.E.S., N.T., A.S. and G.R.A. contributed phenotypes, genotypes and analyses for the MMAP/NEI study. Rotterdam: G.H.S.B., A.G.U., C.M.v.D., J.R.V. and C.C.W.K. contributed phenotypes, genotypes and analyses for the Rotterdam study. SAGE: T.A., C.-Y.C., B.K.C. and E.N.V. contributed phenotypes, genotypes and analyses for the SAGE study. Southern German AMD Study: L.G.F., C.G., C.H., C.N.K., P.L., T.M., G.R., H.-E.W., T.W.W., B.H.F.W. and I.M.H. contributed phenotypes, genotypes and analyses for the Southern German AMD Study. Tufts/Massachusetts General Hospital: Y.Y., S.R., K.A.C., M.J.D., E.E., J.F., J.P.A.I., R. Reynolds, L.S. and J.M.S. contributed phenotypes, genotypes and analyses for the Tufts/MGH study. UK Cambridge/Edinburgh: V.C., A.M.A., P.N. Bishop, D.G.C., B.D., S.P.H., J.C.K., A.T.M., H. Shahid, A.F.W. and J.R.W.Y. contributed phenotypes, genotypes and analyses for the UK Cambridge/Edinburgh study. University of Pittsburgh/UCLA: D.E.W., Y.P.C., M.C.O. and M.B.G. contributed phenotypes, genotypes and analyses for the University of Pittsburgh/UCLA study. UCSD: G. Hannum, H.A.F., G. Hughes, I.K., C.J.L., M.Z., L.Z. and K.Z. contributed phenotypes, genotypes and analyses for the USCD study. VRF: R.J.G., L.V., R.P.I. and S.K.I. contributed phenotypes, genotypes and analyses for the VRF study. Gene expression and RNA sequencing data: data were contributed and analyzed by M. Brooks, J.S.F., N.G., R.R.P. and A.S.

Competing financial interests

A.A., G.R.A., K.E.B., V.C., Y.P.C., M.J.D., A.O.E., L.G.F., M.B.G., J.L.H., A.T.M., D.A.S., W.K.S., J.M.S., A.S., B.H.F.W., D.E.W. and J.R.W.Y. are coinventors or beneficiaries of patents related to genetic discoveries in AMD. J.L.H. and M.M.D. are shareholders in ArcticDX. S.G.S. is a consultant for Alimera, Bausch + Lomb, Eyetech and ThromboGenics and receives royalties from IC Labs. U.T., K.S., G.T. and H. Stefansson are affiliated and/or employed by deCODE Genetics and own stock and/or stock options in the company. H.P.N.S. is on advisory boards for Sanofi-Fovea and AMD Therapy Fund and on the safety monitoring board of StemCells Inc. P.M. is on advisory boards for Allergan, Bayer, Novartis, Pfizer and Solvay and has received travel, honorarium and research support from these companies; he has no stock, equity, contract of employment or named position on company boards.

Corresponding authors

Correspondence to:

Author details

Supplementary information

PDF files

  1. Supplementary Text and Figures (3 MB)

    Supplementary Figures 1–4, Supplementary Tables 1–11 and Supplemetnary Note

Additional data