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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

Wang A 1 , Shen J 1 , Rodriguez AA 2 , Saunders EJ 3 , Chen F 1 , Janivara R 4 Show all authors , Darst BF 1 , Sheng X 1 , Xu Y 1 , Chou AJ 1 , Benlloch S 5 , Dadaev T 3 , Brook MN 3 , Plym A 6 , Sahimi A 7 , Hoffman TJ 8 , Takahashi A 9 , Matsuda K 10 , Momozawa Y 11 , Fujita M 12 , Laisk T 13 , Figuerêdo J 13 , Muir K 14 , Ito S 15 , Liu X 16 , Biobank Japan Project , Uchio Y 15 , Kubo M 17 , Kamatani Y 16 , Lophatananon A 14 , Wan P 7 , Andrews C 18 , Lori A 19 , Choudhury PP 20 , Schleutker J 21 , Tammela TLJ 22 , Sipeky C 21 , Auvinen A 23 , Giles GG 24 , Southey MC 25 , MacInnis RJ 24 , Cybulski C 26 , Wokolorczyk D 26 , Lubinski J 26 , Rentsch CT 27 , Cho K 28 , Mcmahon BH 29 , Neal DE 30 , Donovan JL 31 , Hamdy FC 32 , Martin RM 31 , Nordestgaard BG 33 , Nielsen SF 33 , Weischer M 34 , Bojesen SE 33 , Røder A 35 , Stroomberg HV 35 , Batra J 36 , Chambers S 37 , Horvath L 38 , Clements JA 39 , Tilly W 40 , Risbridger GP 41 , Gronberg H 6 , Aly M 6 , Szulkin R 6 , Eklund M 6 , Nordstrom T 6 , Pashayan N 42 , Dunning AM 43 , Ghoussaini M 44 , Travis RC 45 , Key TJ 45 , Riboli E 46 , Park JY 47 , Sellers TA 47 , Lin HY 48 , Albanes D 49 , Weinstein S 49 , Cook MB 49 , Mucci LA 50 , Giovannucci E 50 , Lindstrom S 51 , Kraft P 52 , Hunter DJ 53 , Penney KL 54 , Turman C 52 , Tangen CM 55 , Goodman PJ 55 , Thompson IM 56 , Hamilton RJ 57 , Fleshner NE 57 , Finelli A 58 , Parent MÉ 59 , Stanford JL 60 , Ostrander EA 61 , Koutros S 49 , Beane Freeman LE 49 , Stampfer M 54 , Wolk A 62 , Håkansson N 62 , Andriole GL 63 , Hoover RN 49 , Machiela MJ 49 , Sørensen KD 64 , Borre M 65 , Blot WJ 66 , Zheng W 66 , Yeboah ED 67 , Mensah JE 67 , Lu YJ 68 , Zhang HW 69 , Feng N 70 , Mao X 68 , Wu Y 71 , Zhao SC 72 , Sun Z 73 , Thibodeau SN 74 , McDonnell SK 75 , Schaid DJ 75 , West CML 76 , Barnett G 77 , Maier C 78 , Schnoeller T 79 , Luedeke M 78 , Kibel AS 80 , Drake BF 81 , Cussenot O 82 , Cancel-Tassin G 82 , Menegaux F 83 , Truong T 83 , Koudou YA 84 , John EM 85 , Grindedal EM 86 , Maehle L 86 , Khaw KT 87 , Ingles SA 88 , Stern MC 88 , Vega A 89 , Gómez-Caamaño A 90 , Fachal L 89 , Rosenstein BS 91 , Kerns SL 92 , Ostrer H 93 , Teixeira MR 94 , Paulo P 95 , Brandão A 95 , Watya S 96 , Lubwama A 96 , Bensen JT 97 , Butler EN 97 , Mohler JL 98 , Taylor JA 99 , Kogevinas M 100 , Dierssen-Sotos T 101 , Castaño-Vinyals G 100 , Cannon-Albright L 102 , Teerlink CC 102 , Huff CD 103 , Pilie P 104 , Yu Y 103 , Bohlender RJ 103 , Gu J 103 , Strom SS 105 , Multigner L 106 , Blanchet P 107 , Brureau L 107 , Kaneva R 108 , Slavov C 109 , Mitev V 108 , Leach RJ 110 , Brenner H 111 , Chen X 111 , Holleczek B 112 , Schöttker B 111 , Klein EA 113 , Hsing AW 85 , Kittles RA 114 , Murphy AB 115 , Logothetis CJ 104 , Kim J 104 , Neuhausen SL 116 , Steele L 116 , Ding YC 116 , Isaacs WB 117 , Nemesure B 118 , Hennis AJM 118 , Carpten J 119 , Pandha H 120 , Michael A 120 , De Ruyck K 121 , De Meerleer G 122 , Ost P 122 , Xu J 123 , Razack A 124 , Lim J 124 , Teo SH 125 , Newcomb LF 60 , Lin DW 60 , Fowke JH 126 , Neslund-Dudas CM 127 , Rybicki BA 127 , Gamulin M 128 , Lessel D 129 , Kulis T 130 , Usmani N 131 , Abraham A 131 , Singhal S 131 , Parliament M 131 , Claessens F 132 , Joniau S 133 , Van den Broeck T 132 , Gago-Dominguez M 134 , Castelao JE 135 , Martinez ME 136 , Larkin S 137 , Townsend PA 138 , Aukim-Hastie C 139 , Bush WS 140 , Aldrich MC 141 , Crawford DC 140 , Srivastava S 142 , Cullen J 140 , Petrovics G 143 , Casey G 144 , Wang Y 19 , Tettey Y 145 , Lachance J 4 , Tang W 146 , Biritwum RB 145 , Adjei AA 147 , Tay E 145 , Truelove A 148 , Niwa S 148 , Yamoah K 47 , Govindasami K 3 , Chokkalingam AP 149 , Keaton JM 66 , Hellwege JN 66 , Clark PE 150 , Jalloh M 151 , Gueye SM 151 , Niang L 151 , Ogunbiyi O 152 , Shittu O 153 , Amodu O 154 , Adebiyi AO 155 , Aisuodionoe-Shadrach OI 156 , Ajibola HO 156 , Jamda MA 156 , Oluwole OP 156 , Nwegbu M 156 , Adusei B 157 , Mante S 157 , Darkwa-Abrahams A 145 , Diop H 158 , Gundell SM 1 , Roobol MJ 159 , Jenster G 159 , van Schaik RHN 160 , Hu JJ 161 , Sanderson M 162 , Kachuri L 163 , Varma R 164 , McKean-Cowdin R 7 , Torres M 164 , Preuss MH 165 , Loos RJF 165 , Zawistowski M 166 , Zöllner S 166 , Lu Z 7 , Van Den Eeden SK 167 , Easton DF 168 , Ambs S 146 , Edwards TL 66 , Mägi R 13 , Rebbeck TR 18 , Fritsche L 169 , Chanock SJ 49 , Berndt SI 49 , Wiklund F 6 , Nakagawa H 12 , Witte JS 163 , Gaziano JM 28 , Justice AC 27 , Mancuso N 1 , Terao C 16 , Eeles RA 3 , Kote-Jarai Z 3 , Madduri RK 2 , Conti DV 1 , Haiman CA 170

Affiliations 

  • 1 Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
  • 2 Argonne National Laboratory, Lemont, IL, USA
  • 3 The Institute of Cancer Research, London, UK
  • 4 School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA
  • 5 Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
  • 6 Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
  • 7 Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
  • 8 Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
  • 9 Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • 10 Department of Computational Biology and Medical Sciences, Laboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
  • 11 Laboratory for Genotyping Development, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan
  • 12 Laboratory for Cancer Genomics, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan
  • 13 Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
  • 14 Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
  • 15 Department of Orthopaedics, Shimane University, Izumo, Japan
  • 16 Laboratory for Statistical and Translational Genetics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan
  • 17 RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • 18 Harvard TH Chan School of Public Health and Division of Population Sciences, Dana Farber Cancer Institute, Boston, MA, USA
  • 19 Department of Population Science, American Cancer Society, Kennesaw, GA, USA
  • 20 Surveillance & Health Science Department, American Cancer Society, Kennesaw, GA, USA
  • 21 Institute of Biomedicine, University of Turku, Turku, Finland
  • 22 Department of Urology, Tampere University Hospital, Tampere, Finland
  • 23 Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland
  • 24 Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
  • 25 Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
  • 26 International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
  • 27 Yale School of Medicine, New Haven, CT, USA
  • 28 Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
  • 29 Theoretical Biology Division, Los Alamos National Lab, Los Alamos, NM, USA
  • 30 Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headington, UK
  • 31 Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  • 32 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
  • 33 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • 34 Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
  • 35 Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • 36 Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia
  • 37 University of Technology, Sydney, New South Wales, Australia
  • 38 Chris O'Brien Lifehouse, Camperdown, Sydney, New South Wales, Australia
  • 39 Translational Research Institute, Brisbane, Queensland, Australia
  • 40 Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide, Adelaide, South Australia, Australia
  • 41 Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia
  • 42 Department of Applied Health Research, University College London, London, UK
  • 43 Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Laboratory, University of Cambridge, Cambridge, UK
  • 44 Open Targets, Wellcome Sanger Institute, Saffron Walden, UK
  • 45 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  • 46 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
  • 47 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA
  • 48 School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA
  • 49 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA
  • 50 Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
  • 51 Department of Epidemiology, University of Washington, Seattle, WA, USA
  • 52 Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
  • 53 Nuffield Department of Population Health, University of Oxford, Oxford, UK
  • 54 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
  • 55 SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • 56 CHRISTUS Santa Rosa Hospital-Medical Center, San Antonio, TX, USA
  • 57 Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
  • 58 Division of Urology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
  • 59 Epidemiology and Biostatistics Unit, Centre Armand-Frappier Santé Biotechnologie, Laval, Quebec, Canada
  • 60 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • 61 National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
  • 62 Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  • 63 Brady Urological Institute in National Capital Region, Johns Hopkins University, Baltimore, MD, USA
  • 64 Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
  • 65 Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  • 66 Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
  • 67 University of Ghana Medical School, Accra, Ghana
  • 68 Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, London, UK
  • 69 Second Military Medical University, Shanghai, China
  • 70 Wuxi Second Hospital, Nanjing Medical University, Wuxi, China
  • 71 Department of Urology, First Affiliated Hospital, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
  • 72 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China
  • 73 The People's Hospital of Liaoning Proviouce, The People's Hospital of China Medical University, Shenyang, China
  • 74 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • 75 Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
  • 76 Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust, Manchester, UK
  • 77 University of Cambridge Department of Oncology, Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  • 78 Humangenetik Tuebingen, Tuebingen, Germany
  • 79 Department of Urology, University Hospital Ulm, Ulm, Germany
  • 80 Division of Urologic Surgery, Brigham and Womens Hospital, Boston, MA, USA
  • 81 Washington University School of Medicine, St. Louis, MO, USA
  • 82 GRC 5 Predictive Onco-Urology, Sorbonne Université, Paris, France
  • 83 Exposome and Heredity, CESP (UMR 1018), Paris-Saclay Medical School, Paris-Saclay University, Inserm, Gustave Roussy, Villejuif, France
  • 84 Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France
  • 85 Department of Medicine and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
  • 86 Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
  • 87 Clinical Gerontology Unit, University of Cambridge, Cambridge, UK
  • 88 Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA
  • 89 Fundación Pública Galega Medicina Xenómica, Santiago de Compostela, Spain
  • 90 Department of Radiation Oncology, Complexo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain
  • 91 Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • 92 Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
  • 93 Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA
  • 94 Department of Laboratory Genetics, Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center, Porto, Portugal
  • 95 Cancer Genetics Group, IPO Porto Research Center (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center, Porto, Portugal
  • 96 Uro Care, Kampala, Uganda
  • 97 Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  • 98 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  • 99 Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
  • 100 ISGlobal, Barcelona, Spain
  • 101 CIBER Epidemiología y Salud Pública, Madrid, Spain
  • 102 Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
  • 103 Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • 104 Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • 105 The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • 106 Univ Rennes, Inserm, EHESP, Institut de recherche en santé, environnement et travail, Rennes, France
  • 107 CHU de Pointe-à-Pitre, Univ Antilles, Univ Rennes, Inserm, EHESP, Institut de recherche en santé, environnement et travail, Pointe-à-Pitre, France
  • 108 Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia, Bulgaria
  • 109 Department of Urology and Alexandrovska University Hospital, Medical University of Sofia, Sofia, Bulgaria
  • 110 Department of Cell Systems and Anatomy and Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
  • 111 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 112 Saarland Cancer Registry, Saarbrücken, Germany
  • 113 Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA
  • 114 City of Hope Comprehensive Cancer Center, Duarte, CA, USA
  • 115 Department of Urology, Northwestern University, Chicago, IL, USA
  • 116 Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA, USA
  • 117 James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD, USA
  • 118 Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY, USA
  • 119 Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
  • 120 The University of Surrey, Guildford, UK
  • 121 Ghent University, Faculty of Medicine and Health Sciences, Basic Medical Sciences, Ghent, Belgium
  • 122 Department of Radiotherapy, Ghent University Hospital, Ghent, Belgium
  • 123 Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA
  • 124 Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 125 Cancer Research Malaysia, Outpatient Centre, Subang Jaya Medical Centre, Subang Jaya, Malaysia
  • 126 Department of Preventive Medicine, Division of Epidemiology, The University of Tennessee Health Science Center, Memphis, TN, USA
  • 127 Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA
  • 128 Division of Medical Oncology, Urogenital Unit, Department of Oncology, University Hospital Centre Zagreb, Zagreb, Croatia
  • 129 Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 130 Department of Urology, University Hospital Center Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia
  • 131 Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada
  • 132 Department of Cellular and Molecular Medicine, Molecular Endocrinology Laboratory, Leuven, Belgium
  • 133 Department of Urology, University Hospitals Leuven, Leuven, Belgium
  • 134 Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saúde, SERGAS, Santiago de Compostela, Spain
  • 135 Genetic Oncology Unit, CHUVI Hospital, Complexo Hospitalario Universitario de Vigo, Instituto de Investigación Biomédica Galicia Sur, Vigo, Spain
  • 136 Moores Cancer Center, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA
  • 137 Scientific Education Support, Thames Ditton, Surrey, Formerly Cancer Sciences, University of Southampton, Southampton, UK
  • 138 School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK
  • 139 Scientific Education Support, Thames Ditton, UK
  • 140 Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA
  • 141 Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
  • 142 Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington DC, USA
  • 143 Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
  • 144 Department of Public Health Science, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
  • 145 Korle Bu Teaching Hospital, Accra, Ghana
  • 146 Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
  • 147 Department of Pathology, University of Ghana Medical School, Accra, Ghana
  • 148 Westat, Rockville, MD, USA
  • 149 School of Public Health, University of California, Berkeley, Berkeley, CA, USA
  • 150 Atrium Health/Levine Cancer Institute, Charlotte, NC, USA
  • 151 Hôpital Général Idrissa Pouye, Dakar, Senegal
  • 152 Department of Pathology, College of Medicine, University of Ibadan, Ibadan, Nigeria
  • 153 Department of Surgery, College of Medicine, University of Ibadan and Univerity College Hospital, Ibadan, Nigeria
  • 154 Institute of Child Health, College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria
  • 155 Clinical Epidemiology Unit, Department of Community Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria
  • 156 College of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Center, Abuja, Nigeria
  • 157 37 Military Hospital, Accra, Ghana
  • 158 Laboratoires Bacteriologie et Virologie, Hôpital Aristide Le Dantec, Dakar, Senegal
  • 159 Department of Urology, Erasmus University Medical Center, Rotterdam, the Netherlands
  • 160 Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, the Netherlands
  • 161 The University of Miami School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA
  • 162 Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA
  • 163 Department of Epidemiology and Population Health, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
  • 164 Southern California Eye Institute, CHA Hollywood Presbyterian Medical Center, Los Angeles, CA, USA
  • 165 The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • 166 Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
  • 167 Division of Research, Kaiser Permanente, Oakland, CA, USA
  • 168 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK
  • 169 Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA
  • 170 Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. haiman@usc.edu
Nat Genet, 2023 Dec;55(12):2065-2074.
PMID: 37945903 DOI: 10.1038/s41588-023-01534-4

Abstract

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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