Article | Published:

Large-scale genotyping identifies 41 new loci associated with breast cancer risk

Nature Genetics volume 45, pages 353361 (2013) | Download Citation

Abstract

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for 9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10−8). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility.

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Acknowledgements

The authors wish to thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. BCAC is funded by Cancer Research UK (C1287/A10118 and C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of BCAC have been funded by the European Union European Cooperation in Science and Technology (COST) programme (BM0606). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining the GWAS data was supported in part by the US National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative grant 1 U19 CA 148065-01 (DRIVE, part of the GAME-ON initiative). A full description of funding and acknowledgments is provided in the Supplementary Note.

Author information

Author notes

    • Kyriaki Michailidou
    •  & Per Hall

    These authors contributed equally to this work.

Affiliations

  1. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    • Kyriaki Michailidou
    • , Joe Dennis
    • , Manjeet K Bolla
    • , Qin Wang
    • , Andrew Lee
    • , Robert Luben
    • , Judith Brown
    • , Paul D P Pharoah
    •  & Douglas F Easton
  2. Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    • Per Hall
    • , Kamila Czene
    • , Nils Schoof
    •  & Keith Humphreys
  3. Human Genotyping Unit–Centro Nacional de Genotipado (CEGEN), Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

    • Anna Gonzalez-Neira
    • , Guillermo Pita
    • , M Rosario Alonso
    •  & Javier Benitez
  4. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

    • Maya Ghoussaini
    • , Ed Dicks
    • , Mitul Shah
    • , Craig Luccarini
    • , Paul D P Pharoah
    • , Alison M Dunning
    •  & Douglas F Easton
  5. Genetic & Molecular Epidemiology Group, Human Cancer Genetics Programme, CNIO, Madrid, Spain.

    • Roger L Milne
  6. Division of Molecular Pathology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

    • Marjanka K Schmidt
    • , Annegien Broeks
    •  & Laura J Van't Veer
  7. Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

    • Marjanka K Schmidt
  8. Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

    • Jenny Chang-Claude
    • , Rebecca Hein
    • , Anja Rudolph
    • , Stefan Nickels
    •  & Dieter Flesch-Janys
  9. Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.

    • Stig E Bojesen
    • , Børge G Nordestgaard
    •  & Sune F Nielsen
  10. Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.

    • Stig E Bojesen
    • , Børge G Nordestgaard
    •  & Sune F Nielsen
  11. Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK.

    • Clare Turnbull
    • , Nazneen Rahman
    • , Anthony Swerdlow
    • , Michael Jones
    •  & Montse Garcia-Closas
  12. Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK.

    • Olivia Fletcher
    • , Nichola Johnson
    • , Alan Ashworth
    • , Nick Orr
    •  & Montse Garcia-Closas
  13. Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.

    • Julian Peto
    • , Lorna Gibson
    • , Isabel dos Santos Silva
    •  & Zoe Aitken
  14. Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

    • Heli Nevanlinna
    • , Taru A Muranen
    • , Kirsimari Aaltonen
    •  & Tuomas Heikkinen
  15. Department of Clinical Genetics, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

    • Kristiina Aittomäki
    •  & Kirsimari Aaltonen
  16. Department of Oncology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

    • Carl Blomqvist
    •  & Kirsimari Aaltonen
  17. Human Genetics Division, Genome Institute of Singapore, Singapore.

    • Astrid Irwanto
    • , Jianjun Liu
    •  & Jingmei Li
  18. Section of Oncogenetics, Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.

    • Quinten Waisfisz
    • , Hanne Meijers-Heijboer
    •  & Muriel Adank
  19. Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.

    • Rob B van der Luijt
  20. PMV (Primär Medizinische Versorgung) Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.

    • Rebecca Hein
  21. Department of Psychiatry, University of Mainz, Mainz, Germany.

    • Norbert Dahmen
  22. Institute for Quality and Efficiency in Health Care (IQWiG), Cologne, Germany.

    • Lars Beckman
  23. Division for Gynaecological Tumor Genetics, Clinic of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany.

    • Alfons Meindl
  24. Centre of Familial Breast and Ovarian Cancer, University of Cologne, Cologne, Germany.

    • Rita K Schmutzler
  25. Centre for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.

    • Rita K Schmutzler
  26. Max Planck Institute of Psychiatry, Munich, Germany.

    • Bertram Müller-Myhsok
  27. Institute of Human Genetics, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Peter Lichtner
  28. Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, Melbourne School of Population Health, The University of Melbourne, Melbourne, Victoria, Australia.

    • John L Hopper
    • , Enes Makalic
    • , Daniel F Schmidt
    • , Quang M Bui
    • , Jennifer Stone
    • , Gillian S Dite
    • , Carmel Apicella
    • , Graham G Giles
    • , Gianluca Severi
    •  & Laura Baglietto
  29. Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia.

    • Melissa C Southey
    •  & Helen Tsimiklis
  30. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Andre G Uitterlinden
  31. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Albert Hofman
  32. Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • David J Hunter
  33. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.

    • Stephen J Chanock
    • , Jonine Figueroa
    •  & Louise Brinton
  34. McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.

    • Daniel Vincent
    • , François Bacot
    •  & Daniel C Tessier
  35. Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

    • Sander Canisius
    •  & Lodewyk F A Wessels
  36. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

    • Christopher A Haiman
    • , Brian E Henderson
    • , Fredrick Schumacher
    • , Anna H Wu
    • , Chiu-Chen Tseng
    • , David Van Den Berg
    •  & Daniel O Stram
  37. Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.

    • Henrik Flyger
  38. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.

    • Fergus J Couch
    •  & Xianshu Wang
  39. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.

    • Celine Vachon
    • , Kristen N Stevens
    •  & Susan Slager
  40. Vesalius Research Center (VRC), VIB, Leuven, Belgium.

    • Diether Lambrechts
    •  & Matthieu Moisse
  41. Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium.

    • Diether Lambrechts
    •  & Matthieu Moisse
  42. Department of Oncology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium.

    • Robert Paridaens
    •  & Marie-Rose Christiaens
  43. Department of Cancer Epidemiology/Clinical Cancer Registry, University Clinic Hamburg-Eppendorf, Hamburg, Germany.

    • Dieter Flesch-Janys
  44. Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany.

    • Dieter Flesch-Janys
  45. Sanquin Research, Amsterdam, The Netherlands.

    • C Ellen van der Schoot
  46. INSERM (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, Villejuif, France.

    • Pascal Guénel
    • , Thérèse Truong
    •  & Florence Menegaux
  47. Unité Mixte de Recherche Scientifique (UMRS) 1018, University Paris–Sud, Villejuif, France.

    • Pascal Guénel
    • , Thérèse Truong
    •  & Florence Menegaux
  48. UMRS 775, INSERM, Université Paris Sorbonne Cité, Paris, France.

    • Pierre Laurent-Puig
  49. Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.

    • Frederik Marme
    • , Andreas Schneeweiss
    • , Christof Sohn
    •  & Barbara Burwinkel
  50. National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.

    • Frederik Marme
    •  & Andreas Schneeweiss
  51. Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    • Barbara Burwinkel
  52. Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain.

    • M Pilar Zamora
  53. Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain.

    • Jose Ignacio Arias Perez
  54. Cancer Research UK/Yorkshire Cancer Research Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield, UK.

    • Angela Cox
    • , Ian W Brock
    •  & Malcolm W R Reed
  55. Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.

    • Simon S Cross
  56. Division of Cancer Studies, National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's & St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London, London, UK.

    • Elinor J Sawyer
  57. Welcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Ian Tomlinson
  58. Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.

    • Ian Tomlinson
  59. Clinical Science Institute, University Hospital Galway, Galway, Ireland.

    • Michael J Kerin
    •  & Nicola Miller
  60. University of Hawaii Cancer Center, Honolulu, Hawaii, USA.

    • Loic Le Marchand
  61. Ontario Cancer Genetics Network, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

    • Irene L Andrulis
    •  & Gord Glendon
  62. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

    • Irene L Andrulis
  63. Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

    • Julia A Knight
  64. Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

    • Julia A Knight
  65. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.

    • Anna Marie Mulligan
  66. Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.

    • Anna Marie Mulligan
  67. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

    • Annika Lindblom
  68. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

    • Sara Margolin
  69. Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Maartje J Hooning
    • , Antoinette Hollestelle
    •  & Agnes Jager
  70. Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Ans M W van den Ouweland
  71. Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria, Australia.

    • Graham G Giles
    • , Gianluca Severi
    •  & Laura Baglietto
  72. University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen–Nuremberg, Erlangen, Germany.

    • Peter A Fasching
    • , Lothar Haeberle
    •  & Matthias W Beckmann
  73. Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • Peter A Fasching
  74. Institute of Human Genetics, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.

    • Arif B Ekici
  75. Division of Clinical Epidemiology and Aging Research, DKFZ, Heidelberg, Germany.

    • Hermann Brenner
    • , Heiko Müller
    •  & Volker Arndt
  76. Saarland Cancer Registry, Saarbrücken, Germany.

    • Christa Stegmaier
  77. Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.

    • Alan Ashworth
    • , Nick Orr
    •  & Montse Garcia-Closas
  78. Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.

    • Jolanta Lissowska
  79. Department of Medicine, McGill University, Montreal, Quebec, Canada.

    • Mark S Goldberg
  80. Division of Clinical Epidemiology, McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada.

    • Mark S Goldberg
  81. Département de Médecine Sociale et Préventive, Département de Santé Environnementale et Santé au Travail, Université de Montréal, Montreal, Quebec, Canada.

    • France Labrèche
  82. Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Quebec, Canada.

    • Martine Dumont
    •  & Jacques Simard
  83. Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital, Oulu, Finland.

    • Robert Winqvist
    •  & Katri Pylkäs
  84. Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland.

    • Arja Jukkola-Vuorinen
  85. Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland.

    • Mervi Grip
  86. Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.

    • Hiltrud Brauch
  87. University of Tübingen, Tübingen, Germany.

    • Hiltrud Brauch
  88. Molecular Genetics of Breast Cancer, DKFZ, Heidelberg, Germany.

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  89. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr–Universität Bochum (IPA), Bochum, Germany.

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    • Paolo Radice
    •  & Paolo Peterlongo
  91. Istituto FIRC di Oncologia Molecolare (IFOM), Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.

    • Paolo Radice
    •  & Paolo Peterlongo
  92. Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS INT, Milan, Italy.

    • Siranoush Manoukian
  93. Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy.

    • Bernardo Bonanni
  94. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.

    • Peter Devilee
  95. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

    • Peter Devilee
  96. Department of Surgical Oncology, Leiden University Medical Center, Leiden, The Netherlands.

    • Rob A E M Tollenaar
  97. Family Cancer Clinic, Department of Medical Oncology, Erasmus Medical Center–Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.

    • Caroline Seynaeve
  98. Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.

    • Christi J van Asperen
  99. Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

    • Anna Jakubowska
    • , Jan Lubinski
    • , Katarzyna Jaworska
    •  & Katarzyna Durda
  100. Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland.

    • Katarzyna Jaworska
  101. School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.

    • Arto Mannermaa
    • , Veli-Matti Kosma
    •  & Jaana M Hartikainen
  102. Biocenter Kuopio, Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland.

    • Arto Mannermaa
    • , Veli-Matti Kosma
    •  & Jaana M Hartikainen
  103. Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.

    • Arto Mannermaa
    • , Vesa Kataja
    • , Veli-Matti Kosma
    •  & Jaana M Hartikainen
  104. School of Medicine, Institute of Clinical Medicine and Oncology, University of Eastern Finland, Kuopio, Finland.

    • Vesa Kataja
  105. Cancer Center, Kuopio University Hospital, Kuopio, Finland.

    • Vesa Kataja
  106. Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.

    • Natalia V Bogdanova
    •  & Thilo Dörk
  107. Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.

    • Natalia V Bogdanova
  108. NN Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.

    • Natalia N Antonenkova
  109. Institute for Clinical Epidemiology and Molecular Biology (EpiGen), Faculty of Medicine, University of Oslo, Oslo, Norway.

    • Vessela N Kristensen
  110. Group of Cancer Genome Variation, Department of Genetics, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet, Oslo, Norway.

    • Vessela N Kristensen
  111. Department of Epidemiology, University of California–Irvine, Irvine, California, USA.

    • Hoda Anton-Culver
  112. Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.

    • Amanda E Toland
  113. Roswell Park Cancer Institute, Buffalo, New York, USA.

    • Stephen Edge
  114. Molecular Diagnostics Laboratory, Institute of Radioisotopes and Radiodiagnostic Products (IRRP), National Centre for Scientific Research Demokritos, Aghia Paraskevi Attikis, Athens, Greece.

    • Florentia Fostira
  115. Seoul National University College of Medicine, Seoul, Korea.

    • Daehee Kang
    • , Keun-Young Yoo
    •  & Dong-Young Noh
  116. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.

    • Keitaro Matsuo
    • , Hidemi Ito
    •  & Aiko Sueta
  117. Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.

    • Hiroji Iwata
  118. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Xiao-Ou Shu
    • , Hui Cai
    • , William J Blot
    • , Lisa B Signorello
    • , Qiuyin Cai
    • , Wei Zheng
    • , Sandra Deming-Halverson
    • , Martha Shrubsole
    •  & Jirong Long
  119. Shanghai Center for Disease Control and Prevention, Shanghai, China.

    • Wei Lu
  120. Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.

    • Yu-Tang Gao
  121. Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia.

    • Soo Hwang Teo
    •  & Sze Yee Phuah
  122. Breast Cancer Research Unit, University Malaya Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia.

    • Soo Hwang Teo
    •  & Cheng Har Yip
  123. Singapore Eye Research Institute, National University of Singapore, Singapore.

    • Belinda K Cornes
  124. Saw Swee Hock School of Public Health, National University of Singapore, Singapore.

    • Mikael Hartman
    • , Hui Miao
    •  & Wei Yen Lim
  125. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

    • Mikael Hartman
    •  & Jen-Hwei Sng
  126. Warwick Medical School, University of Warwick, Coventry, UK.

    • Kenneth Muir
    • , Artitaya Lophatananon
    •  & Sarah Stewart-Brown
  127. Ministry of Public Health, Bangkok, Thailand.

    • Pornthep Siriwanarangsan
  128. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

    • Chen-Yang Shen
    •  & Chia-Ni Hsiung
  129. Colleague of Public Health, China Medical University, Taichong, Taiwan.

    • Chen-Yang Shen
  130. Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

    • Pei-Ei Wu
  131. Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan.

    • Shian-Ling Ding
  132. National Cancer Institute, Bangkok, Thailand.

    • Suleeporn Sangrajrang
  133. International Agency for Research on Cancer, Lyon, France.

    • Valerie Gaborieau
    • , Paul Brennan
    •  & James McKay
  134. International Epidemiology Institute, Rockville, Maryland, USA.

    • William J Blot
    •  & Lisa B Signorello
  135. Department of Genetics, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.

    • Georgia Chenevix-Trench
  136. Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain.

    • Javier Benitez

Consortia

  1. The Breast and Ovarian Cancer Susceptibility Collaboration

    A list of members is provided in the Supplementary Note.

  2. Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON)

    A list of members is provided in the Supplementary Note.

  3. kConFab Investigators

    A list of members is provided in the Supplementary Note.

  4. Australian Ovarian Cancer Study Group

    A list of members is provided in the Supplementary Note.

  5. The GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network

    A list of members is provided in the Supplementary Note.

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Contributions

K. Michailidou and D.F.E. performed the statistical analysis and drafted the manuscript. D.F.E. conceived and coordinated the synthesis of the iCOGS array and led BCAC. P.H. coordinated COGS. J. Benitez led the iCOGS genotyping working group. A.G.-N., G.P., M.R.A., J. Benitez, D.V., F.B., D.C.T., J. Simard, A.M.D. and C.L. coordinated genotyping of the iCOGS array. M.G.-C., P.D.P.P. and M.K.S. led the BCAC pathology and survival working group. J.C.-C. led the BCAC risk factor working group. A.M.D. and G.C.-T. led the iCOGS quality control working group. J.D., E.D., M. Ghoussaini and A. Lee provided bioinformatics support. M.K.B. and Q. Wang provided data management support for BCAC. S.C. and L.F.A.W. provided analysis of the TCGA expression data. C.T., N.R. and D.F.E. led the UK2 GWAS. O.F., J.P. and I.d.S.S. led the BBCS GWAS. H.N., T.A.M., K. Aittomäki and C.B. led the HEBCS GWAS. P.H., K.C., A.I. and J. Liu led the SASBAC GWAS. Q. Waisfisz, H.M.-H., M.A. and R.B.v.d.L. led the DFBBCS GWAS. J.C.-C., R.H., N.D. and L. Beckman led the MARIE GWAS. A. Meindl, R.K.S., B.M.-M. and P.L. led the GC-HBOC GWAS. J.L.H., M.C.S., E.M., D.F.S. and H.T. led the ABCFS GWAS. A.G.U. and A. Hofman led the genotyping in the Rotterdam study. D.J.H. and S.J.C. led the CGEMS GWAS. F.J.C. and S. Slager coordinated TNBCC. C.A.H., B.E.H., F.S. and L.L.M. coordinated MEC. P.D.P.P., D.F.E. and M. Shah coordinated SEARCH. R.L. coordinated EPIC-Norfolk. J. Brown coordinated SIBS. P.H., K.C., N.S., K.H. and J. Li coordinated SASBAC and pKARMA. S.E.B., B.G.N., S.F.N. and H.F. coordinated CGPS. F.J.C., X.W., C.V. and K.N.S. coordinated MCBCS. D.L., M.M., R.P. and M.-R.C. coordinated LMBC. J.C.-C., A.R., S.N. and D.F.-J. coordinated MARIE. N.J., L.G. and Z.A. coordinated BBCS. K. Aaltonen and T.H. coordinated HEBCS. M.K.S., A.B., L.J.V.t.V. and C.E.v.d.S. coordinated ABCS. P.G., T.T., P.L.-P. and F. Menegaux coordinated CECILE. F. Marme, A. Schneeweiss, C. Sohn and B. Burwinkel coordinated BSUCH. R.L.M., A.G.-N., M.P.Z., J.I.A.P. and J. Benitez coordinated CNIO-BCS. A.C., I.W.B., S.S.C. and M.W.R.R. coordinated SBCS. E.J.S., I.T., M.J.K. and N.M. coordinated BIGGS. I.L.A., J.A.K., G.G. and A.M.M. coordinated OFBCR. A. Lindblom and S. Margolin coordinated KARBAC. M.J.H., A. Hollestelle, A.M.W.v.d.O. and A. Jager coordinated RBCS. J.L.H., M.C.S., Q.M.B., J. Stone, G.S.D. and C.A. coordinated ABCFS. J.L.H., M.C.S., G.G.G., G.S. and L. Baglietto coordinated MCCS. P.A.F., L.H., A.B.E. and M.W.B. coordinated BBCC. H. Brenner, H. Müller, V.A. and C. Stegmaier coordinated ESTHER. A. Swerdlow, A.A., N.O., M.J. and M.G.-C. coordinated UKBGS. M.G.-C., J.F., J. Lissowska and L. Brinton coordinated PBCS. M.S.G., F.L., M.D. and J. Simard coordinated MTLGEBCS. R.W., K.P., A.J.-V. and M. Grip coordinated OBCS. H. Brauch, U.H. and T.B. coordinated GENICA. P.R., P.P., S. Manoukian and B. Bonanni coordinated MBCSG. P.D., R.A.E.M.T., C. Seynaeve and C.J.v.A. coordinated ORIGO. A. Jakubowska, J. Lubinski, K.J. and K.D. coordinated SZBCS. A. Mannermaa, V.K., V.-M.K. and J.M.H. coordinated KBCP. N.V.B., N.N.A. and T.D. coordinated HMBCS. V.N.K. coordinated NBCS. H.A.-C. coordinated UCIBCS. A.E.T. coordinated OSU. S.E. coordinated RPCI. F.F. coordinated DEMOKRITOS. D.K., K.-Y.Y. and D.-Y.N. coordinated SEBCS. K. Matsuo, H. Ito, H. Iwata and A. Sueta coordinated HERPACC. A.H.W., C.-C.T., D.V.D.B. and D.O.S. coordinated LAABC. W.Z., X.-O.S., W.L., Y.-T.G. and H.C. coordinated SGBCS. S.H.T., C.H.Y., S.Y.P. and B.K.C. coordinated MYBRCA. M.H., H. Miao, W.Y.L. and J.-H.S. coordinated SGBCC. K. Muir, A. Lophatananon, S.S.-B. and P.S. coordinated ACP. C.-Y.S., C.-N.H., P.-E.W. and S.-L.D. coordinated TWBCS. S. Sangrajrang, V.G., P.B. and J.M. coordinated TBCS. W.J.B., L.B.S., Q.C. and W.Z. coordinated SCCS. W.Z., S.D.-H., M. Shrubsole and J. Long coordinated NBHS. G.C.-T. coordinated the genotyping component of kConFab. All authors provided critical review of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Per Hall or Douglas F Easton.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–4, Supplementary Tables 1–8 and Supplementary Note

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DOI

https://doi.org/10.1038/ng.2563

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