Article | Published:

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

Nature Genetics volume 47, pages 12941303 (2015) | Download Citation

Abstract

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in 70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (6% increase in risk per year; P = 3 × 10−14), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

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References

  1. 1.

    Genetics of reproductive lifespan. Nat. Genet. 41, 637–638 (2009).

  2. 2.

    , , & Testing ovarian reserve to predict age at menopause. Maturitas 63, 280–291 (2009).

  3. 3.

    & The variability of female reproductive ageing. Hum. Reprod. Update 8, 141–154 (2002).

  4. 4.

    et al. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Nat. Genet. 44, 260–268 (2012).

  5. 5.

    et al. DNA mismatch repair gene MSH6 implicated in determining age at natural menopause. Hum. Mol. Genet. 23, 2490–2497 (2014).

  6. 6.

    et al. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat. Genet. (28 September 2015).

  7. 7.

    & The ovary: anatomy and function throughout human life. Ann. NY Acad. Sci. 1127, 1–9 (2008).

  8. 8.

    et al. Human DNA helicase B (HDHB) binds to replication protein A and facilitates cellular recovery from replication stress. J. Biol. Chem. 287, 6469–6481 (2012).

  9. 9.

    , , , & CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. J. Clin. Oncol. 26, 542–548 (2008).

  10. 10.

    et al. Exome sequencing reveals MCM8 mutation underlies ovarian failure and chromosomal instability. J. Clin. Invest. 125, 258–262 (2015).

  11. 11.

    et al. Ovarian failure related to eukaryotic initiation factor 2B mutations. Am. J. Hum. Genet. 72, 1544–1550 (2003).

  12. 12.

    et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429, 417–423 (2004).

  13. 13.

    et al. Genetic investigation of four meiotic genes in women with premature ovarian failure. Eur. J. Endocrinol. 158, 107–115 (2008).

  14. 14.

    et al. Tdrd3 is a novel stress granule–associated protein interacting with the Fragile-X syndrome protein FMRP. Hum. Mol. Genet. 17, 3236–3246 (2008).

  15. 15.

    et al. GRASP v2.0: an update on the Genome-Wide Repository of Associations between SNPs and phenotypes. Nucleic Acids Res. 43, D799–D804 (2015).

  16. 16.

    et al. Body mass index, exercise, and other lifestyle factors in relation to age at natural menopause: analyses from the Breakthrough Generations study. Am. J. Epidemiol. 175, 998–1005 (2012).

  17. 17.

    et al. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. Nature 514, 92–97 (2014).

  18. 18.

    Collaborative Group on Hormonal Factors in Breast Cancer. Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol. 13, 1141–1151 (2012).

  19. 19.

    et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a Mendelian randomisation study. Lancet Diabetes Endocrinol. 2, 719–729 (2014).

  20. 20.

    et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat. Genet. 45, 353–361 (2013).

  21. 21.

    , , , & Rare variants create synthetic genome-wide associations. PLoS Biol. 8, e1000294 (2010).

  22. 22.

    & Lessons from postgenome-wide association studies: functional analysis of cancer predisposition loci. J. Intern. Med. 274, 414–424 (2013).

  23. 23.

    , & Inherited genetic susceptibility to breast cancer: the beginning of the end or the end of the beginning? Am. J. Pathol. 183, 1038–1051 (2013).

  24. 24.

    et al. Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans. Sci. Transl. Med. 5, 172ra21 (2013).

  25. 25.

    et al. BRCA1 inhibition of estrogen receptor signaling in transfected cells. Science 284, 1354–1356 (1999).

  26. 26.

    et al. RAP80-directed tuning of BRCA1 homologous recombination function at ionizing radiation–induced nuclear foci. Genes Dev. 25, 685–700 (2011).

  27. 27.

    et al. Multiple regulation of Rad51-mediated homologous recombination by fission yeast Fbh1. PLoS Genet. 10, e1004542 (2014).

  28. 28.

    et al. FBH1 helicase disrupts RAD51 filaments in vitro and modulates homologous recombination in mammalian cells. J. Biol. Chem. 288, 34168–34180 (2013).

  29. 29.

    , & Playing the end game: DNA double-strand break repair pathway choice. Mol. Cell 47, 497–510 (2012).

  30. 30.

    et al. MCM9 mutations are associated with ovarian failure, short stature, and chromosomal instability. Am. J. Hum. Genet. 95, 754–762 (2014).

  31. 31.

    , , & Association of BRCA1 mutations with occult primary ovarian insufficiency: a possible explanation for the link between infertility and breast/ovarian cancer risks. J. Clin. Oncol. 28, 240–244 (2010).

  32. 32.

    et al. Do BRCA1 and BRCA2 mutation carriers have earlier natural menopause than their noncarrier relatives? Results from the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer. J. Clin. Oncol. 31, 3920–3925 (2013).

  33. 33.

    et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. J. Am. Med. Assoc. 310, 1353–1368 (2013).

  34. 34.

    & Cancer risks among BRCA1 and BRCA2 mutation carriers. Br. J. Cancer 96, 11–15 (2007).

  35. 35.

    Menopause and the human hypothalamus: evidence for the role of kisspeptin/neurokinin B neurons in the regulation of estrogen negative feedback. Peptides 30, 111–122 (2009).

  36. 36.

    & Approach to the patient with hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 98, 1781–1788 (2013).

  37. 37.

    et al. Expression of neurokinin B/NK3 receptor and kisspeptin/KISS1 receptor in human granulosa cells. Hum. Reprod. 29, 2736–2746 (2014).

  38. 38.

    et al. Kisspeptin receptor haplo-insufficiency causes premature ovarian failure despite preserved gonadotropin secretion. Endocrinology 155, 3088–3097 (2014).

  39. 39.

    & The DNA damage response in human biology and disease. Nature 461, 1071–1078 (2009).

  40. 40.

    , & METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190–2191 (2010).

  41. 41.

    et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).

  42. 42.

    et al. A comparative analysis of family-based and population-based association tests using whole genome sequence data. BMC Proc. 8, S33 (2014).

  43. 43.

    , , & GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76–82 (2011).

  44. 44.

    , , & Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263–265 (2005).

  45. 45.

    et al. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet. 5, e1000534 (2009).

  46. 46.

    et al. Synthesis of 53 tissue and cell line expression QTL datasets reveals master eQTLs. BMC Genomics 15, 532 (2014).

  47. 47.

    et al. Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits. PLoS Genet. 6, e1001058 (2010).

  48. 48.

    et al. Integrative annotation of chromatin elements from ENCODE data. Nucleic Acids Res. 41, 827–841 (2013).

  49. 49.

    et al. A high-resolution map of human evolutionary constraint using 29 mammals. Nature 478, 476–482 (2011).

  50. 50.

    et al. Super-enhancers in the control of cell identity and disease. Cell 155, 934–947 (2013).

  51. 51.

    et al. An atlas of active enhancers across human cell types and tissues. Nature 507, 455–461 (2014).

  52. 52.

    et al. Chromatin marks identify critical cell types for fine mapping complex trait variants. Nat. Genet. 45, 124–130 (2013).

  53. 53.

    Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427 (2014).

  54. 54.

    , , , & Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat. Genet. 44, 955–959 (2012).

  55. 55.

    1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56–65 (2012).

  56. 56.

    International Consortium for Blood Pressure Genome-Wide Association Studies. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478, 103–109 (2011).

  57. 57.

    et al. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat. Genet. 45, 385–391 (2013).

  58. 58.

    Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381, 1371–1379 (2013).

  59. 59.

    et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet. (28 September 2015).

  60. 60.

    et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat. Genet. 42, 937–948 (2010).

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Acknowledgements

For full acknowledgments, see the Supplementary Note.

Author information

Author notes

    • Felix R Day
    • , Katherine S Ruth
    •  & Deborah J Thompson

    These authors contributed equally to this work.

    • Joanne M Murabito
    • , John R B Perry
    •  & Anna Murray

    These authors jointly supervised this work.

Affiliations

  1. Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.

    • Felix R Day
    • , Cathy E Elks
    • , Claudia Langenberg
    • , Jian'an Luan
    • , Robert A Scott
    • , Nicholas J Wareham
    • , Ken K Ong
    •  & John R B Perry
  2. Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.

    • Katherine S Ruth
    • , Samuel E Jones
    •  & Anna Murray
  3. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    • Deborah J Thompson
    • , Antonis C Antoniou
    • , Manjeet K Bolla
    • , Joe Dennis
    • , Kyriaki Michailidou
    • , Paul D P Pharoah
    • , Ailith Pirie
    • , Qin Wang
    •  & Douglas F Easton
  4. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.

    • Kathryn L Lunetta
  5. National Heart, Lung, and Blood Institute and Boston University's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Kathryn L Lunetta
    • , Andrew D Johnson
    • , Jennifer E Huffman
    • , John D Eicher
    •  & Joanne M Murabito
  6. Estonian Genome Center, University of Tartu, Tartu, Estonia.

    • Natalia Pervjakova
    • , Tõnu Esko
    • , Reedik Mägi
    • , Evelin Mihailov
    • , Lili Milani
    •  & Andres Metspalu
  7. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.

    • Natalia Pervjakova
  8. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Daniel I Chasman
    • , Lynda M Rose
    • , Julie E Buring
    •  & Paul M Ridker
  9. Harvard Medical School, Boston, Massachusetts, USA.

    • Daniel I Chasman
    • , David Karasik
    • , Julie E Buring
    •  & Paul M Ridker
  10. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.

    • Lisette Stolk
    • , Fernando Rivadeneira
    • , André G Uitterlinden
    •  & Jenny A Visser
  11. Netherlands Consortium on Health Aging and National Genomics Initiative, Leiden, the Netherlands.

    • Lisette Stolk
    • , Fernando Rivadeneira
    •  & André G Uitterlinden
  12. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Hilary K Finucane
    • , Immaculata De Vivo
    • , Frank B Hu
    • , David J Hunter
    • , Xin Li
    • , Sara Lindström
    • , Peter Kraft
    •  & Alkes L Price
  13. Department of Mathematics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Hilary K Finucane
  14. deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.

    • Patrick Sulem
    • , Daniel F Gudbjartsson
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson
  15. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

    • Brendan Bulik-Sullivan
    •  & Benjamin M Neale
  16. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Brendan Bulik-Sullivan
    •  & Benjamin M Neale
  17. Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.

    • Brendan Bulik-Sullivan
    •  & Benjamin M Neale
  18. Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.

    • Tõnu Esko
  19. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

    • Tõnu Esko
  20. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

    • Tõnu Esko
    •  & David J Hunter
  21. Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.

    • Nora Franceschini
  22. Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, Indiana, USA.

    • Chunyan He
  23. Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, USA.

    • Chunyan He
  24. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Elisabeth Altmaier
    • , Jennifer Kriebel
    • , Judith Manz
    •  & Christian Gieger
  25. Institute of Genetic Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Elisabeth Altmaier
    • , Eva Albrecht
    • , Martina Müller-Nurasyid
    • , Konstantin Strauch
    •  & Christian Gieger
  26. Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Elisabeth Altmaier
    • , Jennifer Kriebel
    • , Judith Manz
    • , Doris Stöckl
    •  & Christian Gieger
  27. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Jennifer A Brody
    •  & Bruce M Psaty
  28. Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.

    • Lude L Franke
  29. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

    • Jennifer E Huffman
    • , Thibaud S Boutin
    • , Jonathan Marten
    • , James F Wilson
    • , Alan F Wright
    •  & Caroline Hayward
  30. Merck Pharmaceuticals, Boston, Massachusetts, USA.

    • Margaux F Keller
  31. Program in Personalized Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.

    • Patrick F McArdle
    •  & Laura M Yerges-Armstrong
  32. Institute of Genetics and Biophysics, National Research Council, Naples, Italy.

    • Teresa Nutile
    • , Daniela Ruggiero
    • , Rossella Sorice
    •  & Marina Ciullo
  33. Institute of Genetics and Biomedical Research, National Research Council, Cagliari, Italy.

    • Eleonora Porcu
    • , Giorgio Pistis
    • , Serena Sanna
    •  & Laura Crisponi
  34. Department of Biomedical Sciences, University of Sassari, Sassari, Italy.

    • Eleonora Porcu
    •  & Giorgio Pistis
  35. Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.

    • Eleonora Porcu
    • , Gonçalo R Abecasis
    •  & Giorgio Pistis
  36. Institute for Maternal and Child Health, Scientific Institute for Research, Hospitalisation and Health Care 'Burlo Garofolo', Trieste, Italy.

    • Antonietta Robino
    • , Dragana Vuckovic
    • , Caterina Barbieri
    • , Ilaria Gandin
    • , Nicola N Pirastu
    • , Diego Vozzi
    • , Paolo P Gasparini
    •  & Sheila Ulivi
  37. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

    • Ursula M Schick
    • , Charles Kooperberg
    • , Ulrike Peters
    •  & Alex P Reiner
  38. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.

    • Jennifer A Smith
    • , Wei Zhao
    •  & Sharon L R Kardia
  39. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.

    • Alexander Teumer
    •  & Henry Völzke
  40. Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.

    • Michela Traglia
    • , Caterina Barbieri
    • , Corrado Masciullo
    • , Cinzia F Sala
    •  & Daniela Toniolo
  41. Department of Clinical Medical Sciences, Surgical and Health, University of Trieste, Trieste, Italy.

    • Dragana Vuckovic
    • , Ilaria Gandin
    • , Giorgia G Girotto
    • , Nicola N Pirastu
    •  & Paolo P Gasparini
  42. Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.

    • Jie Yao
    • , Yii-Der Ida Chen
    • , Xiuqing Guo
    • , Kent D Taylor
    •  & Jerome I Rotter
  43. Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.

    • Najaf Amin
    • , Albert Hofman
    • , Fernando Rivadeneira
    • , Cornelia M van Duijn
    •  & André G Uitterlinden
  44. Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.

    • Tanguy Corre
    •  & Sven Bergmann
  45. Swiss Institute of Bioinformatics, Lausanne, Switzerland.

    • Tanguy Corre
    •  & Sven Bergmann
  46. Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.

    • Jouke-Jan Hottenga
    • , Gonneke Willemsen
    •  & Dorret I Boomsma
  47. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

    • Massimo Mangino
    •  & Tim D Spector
  48. National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, UK.

    • Massimo Mangino
  49. Icelandic Heart Association, Kopavogur, Iceland.

    • Albert V Smith
    •  & Vilmundur Gudnason
  50. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Albert V Smith
    • , Unnur Thorsteinsdottir
    • , Vilmundur Gudnason
    •  & Kari Stefansson
  51. Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland, USA.

    • Toshiko Tanaka
    •  & Luigi Ferrucci
  52. Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.

    • Irene L Andrulis
  53. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

    • Irene L Andrulis
  54. Department of Epidemiology, University of California–Irvine, Irvine, California, USA.

    • Hoda Anton-Culver
  55. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    • Volker Arndt
    •  & Hermann Brenner
  56. Department of Biostatistics, University of Washington, Seattle, Washington, USA.

    • Alice M Arnold
    •  & Barbara McKnight
  57. Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.

    • Matthias W Beckmann
    •  & Peter A Fasching
  58. Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Alicia Beeghly-Fadiel
    •  & Wei Zheng
  59. Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

    • Javier Benitez
    •  & Anna González-Neira
  60. Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain.

    • Javier Benitez
  61. Beckman Research Institute of City of Hope, Duarte, California, USA.

    • Leslie Bernstein
  62. Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.

    • Suzette J Bielinski
    •  & Janet E Olson
  63. Department of Oncology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

    • Carl Blomqvist
  64. Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA.

    • Eric Boerwinkle
    • , Megan L Grove
    •  & Alanna C Morrison
  65. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

    • Eric Boerwinkle
  66. Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.

    • Natalia V Bogdanova
  67. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

    • Stig E Bojesen
    •  & Børge G Nordestgaard
  68. Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.

    • Stig E Bojesen
    •  & Børge G Nordestgaard
  69. Department of Genetics, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital, Oslo, Norway.

    • Anne-Lise Borresen-Dale
    •  & Vessela Kristensen
  70. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

    • Anne-Lise Borresen-Dale
    •  & Vessela Kristensen
  71. Dr. Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.

    • Hiltrud Brauch
  72. Institute of Clinical Pharmacology, University of Tübingen, Tübingen, Germany.

    • Hiltrud Brauch
  73. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

    • Hiltrud Brauch
    •  & Hermann Brenner
  74. Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    • Hermann Brenner
  75. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance Institute of Ruhr University Bochum (IPA), Bochum, Germany.

    • Thomas Brüning
  76. Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    • Barbara Burwinkel
  77. Molecular Biology of Breast Cancer, Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.

    • Barbara Burwinkel
  78. Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

    • Archie Campbell
    •  & David Porteous
  79. Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.

    • Harry Campbell
    • , Igor Rudan
    •  & James F Wilson
  80. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

    • Stephen J Chanock
  81. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • J Ross Chapman
    •  & Ian Tomlinson
  82. Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

    • Georgia Chenevix-Trench
  83. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.

    • Fergus J Couch
  84. Section of Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Andrea D Coviello
  85. Section of Endocrinology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Andrea D Coviello
  86. Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield, UK.

    • Angela Cox
  87. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    • Kamila Czene
    • , Hatef Darabi
    • , Per Hall
    • , Keith Humphreys
    •  & Jingmei Li
  88. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Immaculata De Vivo
    • , Frank B Hu
    •  & David J Hunter
  89. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA.

    • Ellen W Demerath
  90. Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.

    • Peter Devilee
  91. Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.

    • Peter Devilee
  92. Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.

    • Thilo Dörk
  93. Non-Communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, UK.

    • Isabel dos-Santos-Silva
    •  & Julian Peto
  94. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

    • Alison M Dunning
    • , Paul D P Pharoah
    •  & Douglas F Easton
  95. 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
  96. Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA.

    • Jessica D Faul
    •  & David R Weir
  97. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.

    • Jonine Figueroa
  98. Department of Cancer Epidemiology/Clinical Cancer Registry, University Clinic Hamburg-Eppendorf, Hamburg, Germany.

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

    • Dieter Flesch-Janys
  100. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland, USA.

    • Melissa E Garcia
    •  & Tamara B Harris
  101. Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.

    • Montserrat García-Closas
    • , Minouk J Schoemaker
    •  & Anthony Swerdlow
  102. Division of Cancer Studies, Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK.

    • Montserrat García-Closas
  103. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.

    • Graham G Giles
    • , John L Hopper
    •  & Roger L Milne
  104. Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia.

    • Graham G Giles
    •  & Roger L Milne
  105. Department of Medicine, McGill University, Montreal, Quebec, Canada.

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

    • Mark S Goldberg
  107. Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Mark O Goodarzi
  108. School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.

    • Daniel F Gudbjartsson
  109. Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France.

    • Pascal Guénel
    •  & Thérèse Truong
  110. University Paris–Sud, UMRS 1018, Villejuif, France.

    • Pascal Guénel
    •  & Thérèse Truong
  111. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

    • Christopher A Haiman
    •  & Brian E Henderson
  112. Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    • Ute Hamann
    •  & Maria Kabisch
  113. Musculoskeletal Research Programme, Division of Applied Medicine, University of Aberdeen, Aberdeen, UK.

    • Lynne J Hocking
  114. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.

    • Georg Homuth
    •  & Frank Schmidt
  115. Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, the Netherlands.

    • Maartje J Hooning
    •  & Caroline M Seynaeve
  116. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Frank B Hu
    •  & David J Hunter
  117. State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

    • Jinyan Huang
  118. Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

    • Anna Jakubowska
    •  & Jan Lubinski
  119. Hebrew SeniorLife Institute for Aging Research, Boston, Massachusetts, USA.

    • David Karasik
  120. Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.

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

    • Julia A Knight
  122. Faculty of Medicine, University of Split, Split, Croatia.

    • Ivana Kolcic
    • , Ozren Polasek
    •  & Tatijana Zemunik
  123. Cancer Center, Kuopio University Hospital, Kuopio, Finland.

    • Veli-Matti Kosma
    •  & Arto Mannermaa
  124. School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.

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

    • Veli-Matti Kosma
    •  & Arto Mannermaa
  126. German Center for Diabetes Research, Neuherberg, Germany.

    • Jennifer Kriebel
  127. Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway.

    • Vessela Kristensen
  128. Vesalius Research Center (VRC), VIB, Leuven, Belgium.

    • Diether Lambrechts
  129. Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium.

    • Diether Lambrechts
  130. Center for Human Genetics, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

    • Yongmei Liu
  131. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

    • Sara Margolin
  132. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

    • Nicholas G Martin
    •  & Grant W Montgomery
  133. Division of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany.

    • Alfons Meindl
  134. Department of Medicine I, Ludwig Maximilians University Munich, Munich, Germany.

    • Martina Müller-Nurasyid
  135. German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.

    • Martina Müller-Nurasyid
  136. Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.

    • Michael Nalls
  137. Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

    • Heli Nevanlinna
  138. Department of Oncology, University Hospitals Leuven, Leuven, Belgium.

    • Patrick Neven
  139. Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Anne B Newman
  140. Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Anne B Newman
  141. Department of Clinical and Translational Science, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Anne B Newman
  142. British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

    • Sandosh Padmanabhan
  143. Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy.

    • Paolo Peterlongo
  144. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.

    • Astrid Petersmann
  145. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.

    • Bruce M Psaty
    •  & Alex P Reiner
  146. Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.

    • Bruce M Psaty
  147. Department of Health Services, University of Washington, Seattle, Washington, USA.

    • Bruce M Psaty
  148. Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry, University of Oulu, Oulu, Finland.

    • Katri Pylkäs
    •  & Robert Winqvist
  149. Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland.

    • Katri Pylkäs
    •  & Robert Winqvist
  150. Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.

    • Paolo Radice
  151. Medical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Leslie J Raffel
  152. UCLA Clinical and Translational Science Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Leslie J Raffel
  153. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    • Anja Rudolph
    •  & Jenny Chang-Claude
  154. Research Oncology, Guy's Hospital, King's College London, London, UK.

    • Elinor J Sawyer
  155. National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA.

    • David Schlessinger
  156. Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.

    • Marjanka K Schmidt
  157. Division of Molecular Gyneco-Oncology, Department of Gynecology and Obstetrics, University Hospital of Cologne, Cologne, Germany.

    • Rita K Schmutzler
  158. Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany.

    • Rita K Schmutzler
  159. Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany.

    • Rita K Schmutzler
  160. Centre Hospitalier Universitaire de Québec Research Center, Laval University, Quebec City, Quebec, Canada.

    • Jacques Simard
  161. Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.

    • Melissa C Southey
  162. Chair of Genetic Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians Universität, Munich, Germany.

    • Konstantin Strauch
  163. Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.

    • Anthony Swerdlow
  164. Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.

    • Amanda E Toland
  165. NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK.

    • Ian Tomlinson
  166. Icelandic Cancer Registry, Reykjavik, Iceland.

    • Laufey Tryggvadottir
  167. Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.

    • Stephen T Turner
  168. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

    • Melissa Wellons
  169. Department of Endocrinology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.

    • Bruce B H R Wolffenbuttel
  170. LifeLines Cohort Study and Biobank, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

    • Bruce B H R Wolffenbuttel
  171. Molecular Diagnostics Laboratory, Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research 'Demokritos', Athens, Greece.

    • Drakoulis Yannoukakos
  172. Department of Obstetrics and Gynecology, University Medicine Greifswald, Greifswald, Germany.

    • Marek Zygmunt
  173. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

    • Behrooz Z Alizadeh
  174. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Peter Kraft
  175. Department of Paediatrics, University of Cambridge, Cambridge, UK.

    • Ken K Ong
  176. Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Joanne M Murabito

Consortia

  1. The PRACTICAL Consortium

    A full list of members and affiliations appears in the Supplementary Note.

  2. kConFab Investigators

    A full list of members and affiliations appears in the Supplementary Note.

  3. AOCS Investigators

    A full list of members and affiliations appears in the Supplementary Note.

  4. Generation Scotland

    A full list of members and affiliations appears in the Supplementary Note.

  5. EPIC-InterAct Consortium

    A full list of members and affiliations appears in the Supplementary Note.

  6. LifeLines Cohort Study

    A full list of members and affiliations appears in the Supplementary Note.

Authors

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Contributions

All authors reviewed the original and revised manuscripts. Statistical analysis: F.R.D., K.S.R., D.J.T., K.L.L., N.P., D.I.C., L.S., H.K.F., P.S., B.B.-S., T.E., A.D.J., C.E.E., N.F., C. He, E. Altmaier, J.A.B., L.L.F., J.E.H., S.E.J., M.F.K., P.F.M., T.N., E.P., A. Robino, L.M.R., U.M.S., J.A.S., A.T., M.T., D. Vuckovic, J.Y., W. Zhao, E. Albrecht, N.A., T.C., J.-J.H., M.M., A.V.S., T. Tanaka, J.R.B.P. Sample collection, genotyping and phenotyping: G.R.A., I.L.A., H.A.-C., A.C.A., V.A., A.M.A., C. Barbieri, M.W.B., A.B.-F., J.B., L.B., S.J.B., C. Blomqvist, E.B., N.V.B., S.E.B., M.K.B., A.-L.B.-D., T.S.B., H. Brauch, H. Brenner, T.B., B.B., A. Campbell, H.C., S.J.C., J.R.C., Y.-D.I.C., G.C.-T., F.J.C., A.D.C., A. Cox, K.C., H.D., I.D.V., E.W.D., J.D., P.D., T.D., I.d.-S.-S., A.M.D., J.D.E., P.A.F., J.D.F., J.F., D.F.-J., I.G., M.E.G., M.G.-C., G.G. Giles, G.G. Girotto, M.S.G., A.G.-N., M.O.G., M.L.G., D.F.G., P.G., X.G., C.A.H., P.H., U.H., B.E.H., L.J.H., A.H., G.H., M.J.H., J.L.H., F.B.H., J.H., K.H., D.J.H., A.J., M.K., D.K., J.A.K., I.K., C.K., V.-M.K., J.K., V.K., D.L., C.L., J. Li, X.L., S.L., Y.L., J. Luan, J. Lubinski, R.M., A. Mannermaa, J. Manz, S.M., J. Marten, N.G.M., C.M., A. Meindl, K.M., E.M., L.M., R.L.M., M.M.-N., M.N., B.M.N., H.N., P.N., A.B.N., B.G.N., J.E.O., S.P., P.P., U.P., A. Petersmann, J.P., P.D.P.P., N.N.P., A. Pirie, G.P., O.P., D.P., B.M.P., K.P., P.R., L.J.R., F.R., I.R., A. Rudolph, D.R., C.F.S., S.S., E.J.S., D. Schlessinger, M.K.S., F.S., R.K.S., M.J.S., R.A.S., C.M.S., J.S., R.S., M.C.S., D. Stöckl, K. Strauch, A.S., K.D.T., U.T., A.E.T., I.T., T. Truong, L.T., S.T.T., D. Vozzi, Q.W., M.W., G.W., J.F.W., R.W., B.B.H.R.W., A.F.W., D.Y., T.Z., W. Zheng, M.Z. Individual study principal investigators: S.B., D.I.B., J.E.B., L.F., G.W.M., V.G., T.D.S., C.M.v.D., B.Z.A., M.C., L.C., D.F.E., P.P.G., C.G., T.B.H., C. Hayward, S.L.R.K., P.K., B.M., A. Metspalu, A.C.M., A.P.R., P.M.R., J.I.R., D.T., A.G.U., S.U., H.V., N.J.W., D.R.W., L.M.Y.-A., A.L.P., K. Stefansson, J.A.V., K.K.O., J.C.-C., J.M.M., A. Murray. Working group: F.R.D., K.S.R., D.J.T., K.L.L., N.P., D.I.C., L.S., H.K.F., P.S., B.B.-S., T.E., A.D.J., C.E.E., N.F., C. He, A.L.P., K. Stefansson, J.A.V., K.K.O., J.C.-C., J.M.M., J.R.B.P., A. Murray.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to John R B Perry.

Supplementary information

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  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–5 and Supplementary Note.

Excel files

  1. 1.

    Supplementary Tables 1–27

    Supplementary Tables 1–27.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ng.3412

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