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    Nature communications. 2019 Apr 15. doi: 10.1038/s41467-018-08053-5. pii: 10.1038/s41467-018-08053-5
    Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.
    Ferreira MA1,  Gamazon ER2,  Al-Ejeh F3,  Aittomäki K4,  Andrulis IL5,  Anton-Culver H6,  Arason A7,  Arndt V8,  Aronson KJ9,  Arun BK10,  Asseryanis E11,  Azzollini J12,  Balmaña J13,  Barnes DR14,  Barrowdale D15,  Beckmann MW16,  Behrens S17,  Benitez J18,  Bermisheva M19,  Białkowska K20,  Blomqvist C21,  Bogdanova NV22,  Bojesen SE23,  Bolla MK24,  Borg A25,  Brauch H26,  Brenner H27,  Broeks A28,  Burwinkel B29,  Caldés T30,  Caligo MA31,  Campa D32,  Campbell I33,  Canzian F34,  Carter J35,  Carter BD36,  Castelao JE37,  Chang-Claude J38,  Chanock SJ39,  Christiansen H40,  Chung WK41,  Claes KBM42,  Clarke CL43,  Couch FJ44,  Cox A45,  Cross SS46,  Czene K47,  Daly MB48,  de la Hoya M49,  Dennis J50,  Devilee P51,  Diez O52,  Dörk T53,  Dunning AM54,  Dwek M55,  Eccles DM56,  Ejlertsen B57,  Ellberg C58,  Engel C59,  Eriksson M60,  Fasching PA61,  Fletcher O62,  Flyger H63,  Friedman E64,  Frost D65,  Gabrielson M66,  Gago-Dominguez M67,  Ganz PA68,  Gapstur SM69,  Garber J70,  García-Closas M71,  García-Sáenz JA72,  Gaudet MM73,  Giles GG74,  Glendon G75,  Godwin AK76,  Goldberg MS77,  Goldgar DE78,  González-Neira A79,  Greene MH80,  Gronwald J81,  Guénel P82,  Haiman CA83,  Hall P84,  Hamann U85,  He W86,  Heyworth J87,  Hogervorst FBL88,  Hollestelle A89,  Hoover RN90,  Hopper JL91,  Hulick PJ92,  Humphreys K93,  Imyanitov EN94,  Isaacs C95,  Jakimovska M96,  Jakubowska A97,  James PA98,  Janavicius R99,  Jankowitz RC100,  John EM101,  Johnson N102,  Joseph V103,  Karlan BY104,  Khusnutdinova E105,  Kiiski JI106,  Ko YD107,  Jones ME108,  Konstantopoulou I109,  Kristensen VN110,  Laitman Y111,  Lambrechts D112,  Lazaro C113,  Leslie G114,  Lester J115,  Lesueur F116,  Lindström S117,  Long J118,  Loud JT119,  Lubiński J120,  Makalic E121,  Mannermaa A122,  Manoochehri M123,  Margolin S124,  Maurer T125,  Mavroudis D126,  McGuffog L127,  Meindl A128,  Menon U129,  Michailidou K130,  Miller A131,  Montagna M132,  Moreno F133,  Moserle L134,  Mulligan AM135,  Nathanson KL136,  Neuhausen SL137,  Nevanlinna H138,  Nevelsteen I139,  Nielsen FC140,  Nikitina-Zake L141,  Nussbaum RL142,  Offit K143,  Olah E144,  Olopade OI145,  Olsson H146,  Osorio A147,  Papp J148,  Park-Simon TW149,  Parsons MT150,  Pedersen IS151,  Peixoto A152,  Peterlongo P153,  Pharoah PDP154,  Plaseska-Karanfilska D155,  Poppe B156,  Presneau N157,  Radice P158,  Rantala J159,  Rennert G160,  Risch HA161,  Saloustros E162,  Sanden K163,  Sawyer EJ164,  Schmidt MK165,  Schmutzler RK166,  Sharma P167,  Shu XO168,  Simard J169,  Singer CF170,  Soucy P171,  Southey MC172,  Spinelli JJ173,  Spurdle AB174,  Stone J175,  Swerdlow AJ176,  Tapper WJ177,  Taylor JA178,  Teixeira MR179,  Terry MB180,  Teulé A181,  Thomassen M182,  Thöne K183,  Thull DL184,  Tischkowitz M185,  Toland AE186,  Torres D187,  Truong T188,  Tung N189,  Vachon CM190,  van Asperen CJ191,  van den Ouweland AMW192,  van Rensburg EJ193,  Vega A194,  Viel A195,  Wang Q196,  Wappenschmidt B197,  Weitzel JN198,  Wendt C199,  Winqvist R200,  Yang XR201,  Yannoukakos D202,  Ziogas A203,  Kraft P204,  Antoniou AC205,  Zheng W206,  Easton DF207,  Milne RL208,  Beesley J209,  Chenevix-Trench G210
    Collaborators
    Adlard J Ahmed M Barwell J Brady A Brewer C Cook J Davidson R Donaldson A Eason J Eeles R Evans DG Gregory H Hanson H Henderson A Hodgson S Izatt L Kennedy MJ Lalloo F Miller C Morrison PJ Ong KR Perkins J Porteous ME Rogers MT Side LE Snape K Walker L Harrington PA Arnold N Auber B Bogdanova-Markov N Borde J Caliebe A Ditsch N Dworniczak B Engert S Faust U Gehrig A Hahnen E Hauke J Hentschel J Herold N Honisch E Just W Kast K Larsen M Lemke J Nguyen HP Niederacher D Ott CE Platzer K Pohl-Rescigno E Ramser J Rhiem K Steinemann D Sutter C Varon-Mateeva R Wang-Gohrke S Weber BHF Prieur F Pujol P Sagne C Sevenet N Sobol H Sokolowska J Stoppa-Lyonnet D Venat-Bouvet L Balleine R Baxter R Braye S Carpenter J Dahlstrom J Forbes J Lee SC Marsh D Morey A Pathmanathan N Simpson P Spigelman A Wilcken N Yip D Heemskerk-Gerritsen BAM Rookus MA Seynaeve CM van der Baan FH van der Hout AH van der Kolk LE van der Luijt RB van Deurzen CHM van Doorn HC van Engelen K van Hest L van Os TAM Verhoef S Vogel MJ Wijnen JT Miron A Kapuscinski M Bane A Ross E Buys SS Conner TA
    Author information
    1Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia. Manuel.Ferreira@qimr.edu.au.
    2Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, 37235, USA.
    3Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
    4Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, 00290, Helsinki, Finland.
    5Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
    6Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA, 92617.
    7Department of Pathology, Landspitali University Hospital, 101, Reykjavik, Iceland.
    8Division of Clinical Epidemiology and Aging Research, C070, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
    9Department of Public Health Sciences, and Cancer Research Institute, Queen's University, Kingston, ON, K7L 3N6, Canada.
    10Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
    11Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, 1090, Vienna, Austria.
    12Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133, Milan, Italy.
    13Oncogenetics Group, Vall dHebron Institute of Oncology (VHIO), 8035, Barcelona, Spain.
    14Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    15Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    16Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, 91054, Erlangen, Germany.
    17Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
    18Centro de Investigación en Red de Enfermedades Raras (CIBERER), 46010, Valencia, Spain.
    19Institute of Biochemistry and Genetics, Ufa Federal Research Centre of Russian Academy of Sciences, 450054, Ufa, Russia.
    20Department of Genetics and Pathology, Pomeranian Medical University, 71-252, Szczecin, Poland.
    21Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, 00290, Finland.
    22Department of Radiation Oncology, Hannover Medical School, 30625, Hannover, Germany.
    23Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730, Herlev, Denmark.
    24Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    25Department of Oncology, Lund University and Skåne University Hospital, 222 41, Lund, Sweden.
    26Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376, Stuttgart, Germany.
    27Division of Clinical Epidemiology and Aging Research, C070, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
    28Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 CX, Amsterdam, The Netherlands.
    29Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
    30Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), 28040, Madrid, Spain.
    31Section of Molecular Genetics, Dept. of Laboratory Medicine, University Hospital of Pisa, 56126, Pisa, Italy.
    32Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
    33Research Department, Peter MacCallum Cancer Center, Melbourne, VIC, 3000, Australia.
    34Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
    35Department of Gynaecological Oncology, Chris O'Brien Lifehouse and The University of Sydney, Camperdown, NSW, 2050, Australia.
    36Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA, 30303.
    37Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, 36312, Vigo, Spain.
    38Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
    39Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, 20850, USA.
    40Department of Radiation Oncology, Hannover Medical School, 30625, Hannover, Germany.
    41Departments of Pediatrics and Medicine, Columbia University, New York, NY, 10032, USA.
    42Centre for Medical Genetics, Ghent University, Gent, 9000, Belgium.
    43Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, 2145, Australia.
    44Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
    45Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield, S10 2TN, UK.
    46Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, S10 2TN, UK.
    47Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Stockholm, Sweden.
    48Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.
    49Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), 28040, Madrid, Spain.
    50Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    51Department of Pathology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
    52Oncogenetics Group, Vall dHebron Institute of Oncology (VHIO), 8035, Barcelona, Spain.
    53Gynaecology Research Unit, Hannover Medical School, 30625, Hannover, Germany.
    54Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.
    55Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, W1B 2HW, UK.
    56Faculty of Medicine, University of Southampton, Southampton, SO17 1BJ, UK.
    57Department of Oncology, Rigshospitalet, Copenhagen University Hospital, DK-2100, Copenhagen, Denmark.
    58Department of Cancer Epidemiology, Clinical Sciences, Lund University, 222 42, Lund, Sweden.
    59Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107, Leipzig, Germany.
    60Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Stockholm, Sweden.
    61Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, 91054, Erlangen, Germany.
    62The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, SW7 3RP, UK.
    63Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730, Herlev, Denmark.
    64The Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, 52621, Ramat Gan, Israel.
    65Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    66Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Stockholm, Sweden.
    67Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, 15706, Santiago de Compostela, Spain.
    68Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Centre, UCLA, Los Angeles, CA, 90096-6900, USA.
    69Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA, 30303.
    70Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
    71Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, 20850, USA.
    72Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), 28040, Madrid, Spain.
    73Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA, 30303.
    74Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.
    75Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
    76Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, KS, 66160, USA.
    77Department of Medicine, McGill University, Montréal, QC, H4A 3J1, Canada.
    78Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.
    79Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), 28029, Madrid, Spain.
    80Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, 20850-9772, USA.
    81Department of Genetics and Pathology, Pomeranian Medical University, 71-252, Szczecin, Poland.
    82Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, 94805, Villejuif, France.
    83Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
    84Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Stockholm, Sweden.
    85Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
    86Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Stockholm, Sweden.
    87School of Population and Global Health, The University of Western Australia, Perth, WA, 6009, Australia.
    88Family Cancer Clinic, The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, 1066 CX, The Netherlands.
    89Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, 3015 CN, The Netherlands.
    90Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, 20850, USA.
    91Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia.
    92Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL, 60201, USA.
    93Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Stockholm, Sweden.
    94N.N. Petrov Institute of Oncology. St., Petersburg, 197758, Russia.
    95Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 20007, USA.
    96Research Centre for Genetic Engineering and Biotechnology 'Georgi D. Efremov', Macedonian Academy of Sciences and Arts, Skopje, 1000, Republic of Macedonia.
    97Department of Genetics and Pathology, Pomeranian Medical University, 71-252, Szczecin, Poland.
    98Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, 3000, Australia.
    99Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine, Vilnius University Hospital Santariskiu Clinics, Vilnius, 08410, Lithuania.
    100Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15232, USA.
    101Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94304, USA.
    102The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, SW7 3RP, UK.
    103Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
    104David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
    105Institute of Biochemistry and Genetics, Ufa Federal Research Centre of Russian Academy of Sciences, 450054, Ufa, Russia.
    106Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, 00290, Finland.
    107Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, 53177, Germany.
    108Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SM2 5NG, UK.
    109Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, 15310, Greece.
    110Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, 0379, Norway.
    111The Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, 52621, Ramat Gan, Israel.
    112VIB Center for Cancer Biology, VIB, Leuven, 3001, Belgium.
    113Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Bellvitge Biomedical Research Institute, Catalan Institute of Oncology), CIBERONC, Barcelona, 08908, Spain.
    114Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    115David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
    116Genetic Epidemiology of Cancer team, Inserm U900, Paris, 75005, France.
    117Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, 98195, USA.
    118Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
    119Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, 20850-9772, USA.
    120Department of Genetics and Pathology, Pomeranian Medical University, 71-252, Szczecin, Poland.
    121Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia.
    122Translational Cancer Research Area, University of Eastern Finland, Kuopio, 70210, Finland.
    123Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
    124Department of Oncology, Södersjukhuset, 118 83, Stockholm, Sweden.
    125Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
    126Department of Medical Oncology, University Hospital of Heraklion, Heraklion, 711 10, Greece.
    127Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    128Department of Gynecology and Obstetrics, University of Munich, Campus Großhadern, Munich, 81377, Germany.
    129MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, University College London, London, WC1V 6LJ, UK.
    130Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    131NRG Oncology, Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA.
    132Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, 35128, Italy.
    133Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), 28040, Madrid, Spain.
    134Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, 35128, Italy.
    135Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
    136Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, 19066, USA.
    137Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
    138Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, 00290, Finland.
    139Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, 3000, Belgium.
    140Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DK-2100, Denmark.
    141Latvian Biomedical Research and Study Centre, Riga, LV-1067, Latvia.
    142Cancer Genetics and Prevention Program, University of California San Francisco, San Francisco, CA, 94143-1714, USA.
    143Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
    144Department of Molecular Genetics, National Institute of Oncology, Budapest, 1122, Hungary.
    145Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL, 60637, USA.
    146Department of Cancer Epidemiology, Clinical Sciences, Lund University, 222 42, Lund, Sweden.
    147Centro de Investigación en Red de Enfermedades Raras (CIBERER), 46010, Valencia, Spain.
    148Department of Molecular Genetics, National Institute of Oncology, Budapest, 1122, Hungary.
    149Gynaecology Research Unit, Hannover Medical School, 30625, Hannover, Germany.
    150Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
    151Molecular Diagnostics, Aalborg University Hospital, Aalborg, 9000, Denmark.
    152Department of Genetics, Portuguese Oncology Institute, Porto, 4220-072, Portugal.
    153Genome Diagnostics Program, IFOM - the FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, 20139, Italy.
    154Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    155Research Centre for Genetic Engineering and Biotechnology 'Georgi D. Efremov', Macedonian Academy of Sciences and Arts, Skopje, 1000, Republic of Macedonia.
    156Centre for Medical Genetics, Ghent University, Gent, 9000, Belgium.
    157Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, W1B 2HW, UK.
    158Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, 20133, Italy.
    159Clinical Genetics, Karolinska Institutet, Stockholm, 171 76, Sweden.
    160Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, 35254, Israel.
    161Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, 06510, USA.
    162Department of Oncology, University Hospital of Larissa, Larissa, 411 10, Greece.
    163City of Hope Clinical Cancer Genetics Community Research Network, Duarte, CA, 91010, USA.
    164Research Oncology, Guy's Hospital, King's College London, London, SE1 9RT, UK.
    165Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 CX, Amsterdam, The Netherlands.
    166Center for Hereditary Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, 50937, Germany.
    167Department of Internal Medicine, Division of Oncology, University of Kansas Medical Center, Westwood, KS, 66205, USA.
    168Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
    169Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval, Research Center, Québec City, QC, G1V 4G2, Canada.
    170Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, 1090, Vienna, Austria.
    171Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval, Research Center, Québec City, QC, G1V 4G2, Canada.
    172Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia.
    173Population Oncology, BC Cancer, Vancouver, BC, V5Z 1G1, Canada.
    174Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
    175Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia.
    176Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SM2 5NG, UK.
    177Faculty of Medicine, University of Southampton, Southampton, SO17 1BJ, UK.
    178Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, 27709, USA.
    179Department of Genetics, Portuguese Oncology Institute, Porto, 4220-072, Portugal.
    180Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA.
    181Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute),Catalan Institute of Oncology, CIBERONC, Barcelona, 08908, Spain.
    182Department of Clinical Genetics, Odense University Hospital, Odence C, 5000, Denmark.
    183Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
    184Department of Medicine, Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
    185Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montréal, QC, H4A 3J1, Canada.
    186Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, 43210, USA.
    187Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
    188Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, 94805, Villejuif, France.
    189Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
    190Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, 55905, USA.
    191Department of Clinical Genetics, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
    192Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands.
    193Department of Genetics, University of Pretoria, Arcadia, 0007, South Africa.
    194Fundación Pública galega Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela, Spain.
    195Division of Functional onco-genomics and genetics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, 33081, Italy.
    196Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    197Center for Hereditary Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, 50937, Germany.
    198Clinical Cancer Genomics, City of Hope, Duarte, CA, 91010, USA.
    199Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, 118 83, Sweden.
    200Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, 90570, Finland.
    201Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, 20850, USA.
    202Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, 15310, Greece.
    203Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA, 92617.
    204Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, 02115, MA, USA.
    205Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    206Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
    207Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
    208Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.
    209Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
    210Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
    Abstract

    Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.


    Publikations ID: 30988301
    Quelle: öffnen
     
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