Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers

In cancer many gene variants may contribute to disease etiology, but the impact of a given gene variant may have varied effect size. Here, the authors analyse summary statistics of genome-wide association studies from fourteen cancers, and show the utility of polygenic risk scores may vary depending...

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Main Authors: Yan Dora Zhang, Amber N. Hurson, Haoyu Zhang, Parichoy Pal Choudhury, Douglas F. Easton, Roger L. Milne, Jacques Simard, Per Hall, Kyriaki Michailidou, Joe Dennis, Marjanka K. Schmidt, Jenny Chang-Claude, Puya Gharahkhani, David Whiteman, Peter T. Campbell, Michael Hoffmeister, Mark Jenkins, Ulrike Peters, Li Hsu, Stephen B. Gruber, Graham Casey, Stephanie L. Schmit, Tracy A. O’Mara, Amanda B. Spurdle, Deborah J. Thompson, Ian Tomlinson, Immaculata De Vivo, Maria Teresa Landi, Matthew H. Law, Mark M. Iles, Florence Demenais, Rajiv Kumar, Stuart MacGregor, D. Timothy Bishop, Sarah V. Ward, Melissa L. Bondy, Richard Houlston, John K. Wiencke, Beatrice Melin, Jill Barnholtz-Sloan, Ben Kinnersley, Margaret R. Wrensch, Christopher I. Amos, Rayjean J. Hung, Paul Brennan, James McKay, Neil E. Caporaso, Sonja I. Berndt, Brenda M. Birmann, Nicola J. Camp, Peter Kraft, Nathaniel Rothman, Susan L. Slager, Andrew Berchuck, Paul D. P. Pharoah, Thomas A. Sellers, Simon A. Gayther, Celeste L. Pearce, Ellen L. Goode, Joellen M. Schildkraut, Kirsten B. Moysich, Laufey T. Amundadottir, Eric J. Jacobs, Alison P. Klein, Gloria M. Petersen, Harvey A. Risch, Rachel Z. Stolzenberg-Solomon, Brian M. Wolpin, Donghui Li, Rosalind A. Eeles, Christopher A. Haiman, Zsofia Kote-Jarai, Fredrick R. Schumacher, Ali Amin Al Olama, Mark P. Purdue, Ghislaine Scelo, Marlene D. Dalgaard, Mark H. Greene, Tom Grotmol, Peter A. Kanetsky, Katherine A. McGlynn, Katherine L. Nathanson, Clare Turnbull, Fredrik Wiklund, Breast Cancer Association Consortium (BCAC), Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON), Colon Cancer Family Registry (CCFR), Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (CORECT), Endometrial Cancer Association Consortium (ECAC), Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Melanoma Genetics Consortium (GenoMEL), Glioma International Case-Control Study (GICC), International Lung Cancer Consortium (ILCCO), Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium, International Consortium of Investigators Working on Non-Hodgkin’s Lymphoma Epidemiologic Studies (InterLymph), Ovarian Cancer Association Consortium (OCAC), Oral Cancer GWAS, Pancreatic Cancer Case-Control Consortium (PanC4), Pancreatic Cancer Cohort Consortium (PanScan), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), Renal Cancer GWAS, Testicular Cancer Consortium (TECAC), Stephen J. Chanock, Nilanjan Chatterjee, Montserrat Garcia-Closas
Format: Article
Language:English
Published: Nature Publishing Group 2020-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-020-16483-3
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author Yan Dora Zhang
Amber N. Hurson
Haoyu Zhang
Parichoy Pal Choudhury
Douglas F. Easton
Roger L. Milne
Jacques Simard
Per Hall
Kyriaki Michailidou
Joe Dennis
Marjanka K. Schmidt
Jenny Chang-Claude
Puya Gharahkhani
David Whiteman
Peter T. Campbell
Michael Hoffmeister
Mark Jenkins
Ulrike Peters
Li Hsu
Stephen B. Gruber
Graham Casey
Stephanie L. Schmit
Tracy A. O’Mara
Amanda B. Spurdle
Deborah J. Thompson
Ian Tomlinson
Immaculata De Vivo
Maria Teresa Landi
Matthew H. Law
Mark M. Iles
Florence Demenais
Rajiv Kumar
Stuart MacGregor
D. Timothy Bishop
Sarah V. Ward
Melissa L. Bondy
Richard Houlston
John K. Wiencke
Beatrice Melin
Jill Barnholtz-Sloan
Ben Kinnersley
Margaret R. Wrensch
Christopher I. Amos
Rayjean J. Hung
Paul Brennan
James McKay
Neil E. Caporaso
Sonja I. Berndt
Brenda M. Birmann
Nicola J. Camp
Peter Kraft
Nathaniel Rothman
Susan L. Slager
Andrew Berchuck
Paul D. P. Pharoah
Thomas A. Sellers
Simon A. Gayther
Celeste L. Pearce
Ellen L. Goode
Joellen M. Schildkraut
Kirsten B. Moysich
Laufey T. Amundadottir
Eric J. Jacobs
Alison P. Klein
Gloria M. Petersen
Harvey A. Risch
Rachel Z. Stolzenberg-Solomon
Brian M. Wolpin
Donghui Li
Rosalind A. Eeles
Christopher A. Haiman
Zsofia Kote-Jarai
Fredrick R. Schumacher
Ali Amin Al Olama
Mark P. Purdue
Ghislaine Scelo
Marlene D. Dalgaard
Mark H. Greene
Tom Grotmol
Peter A. Kanetsky
Katherine A. McGlynn
Katherine L. Nathanson
Clare Turnbull
Fredrik Wiklund
Breast Cancer Association Consortium (BCAC)
Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON)
Colon Cancer Family Registry (CCFR)
Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (CORECT)
Endometrial Cancer Association Consortium (ECAC)
Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO)
Melanoma Genetics Consortium (GenoMEL)
Glioma International Case-Control Study (GICC)
International Lung Cancer Consortium (ILCCO)
Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium
International Consortium of Investigators Working on Non-Hodgkin’s Lymphoma Epidemiologic Studies (InterLymph)
Ovarian Cancer Association Consortium (OCAC)
Oral Cancer GWAS
Pancreatic Cancer Case-Control Consortium (PanC4)
Pancreatic Cancer Cohort Consortium (PanScan)
Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL)
Renal Cancer GWAS
Testicular Cancer Consortium (TECAC)
Stephen J. Chanock
Nilanjan Chatterjee
Montserrat Garcia-Closas
spellingShingle Yan Dora Zhang
Amber N. Hurson
Haoyu Zhang
Parichoy Pal Choudhury
Douglas F. Easton
Roger L. Milne
Jacques Simard
Per Hall
Kyriaki Michailidou
Joe Dennis
Marjanka K. Schmidt
Jenny Chang-Claude
Puya Gharahkhani
David Whiteman
Peter T. Campbell
Michael Hoffmeister
Mark Jenkins
Ulrike Peters
Li Hsu
Stephen B. Gruber
Graham Casey
Stephanie L. Schmit
Tracy A. O’Mara
Amanda B. Spurdle
Deborah J. Thompson
Ian Tomlinson
Immaculata De Vivo
Maria Teresa Landi
Matthew H. Law
Mark M. Iles
Florence Demenais
Rajiv Kumar
Stuart MacGregor
D. Timothy Bishop
Sarah V. Ward
Melissa L. Bondy
Richard Houlston
John K. Wiencke
Beatrice Melin
Jill Barnholtz-Sloan
Ben Kinnersley
Margaret R. Wrensch
Christopher I. Amos
Rayjean J. Hung
Paul Brennan
James McKay
Neil E. Caporaso
Sonja I. Berndt
Brenda M. Birmann
Nicola J. Camp
Peter Kraft
Nathaniel Rothman
Susan L. Slager
Andrew Berchuck
Paul D. P. Pharoah
Thomas A. Sellers
Simon A. Gayther
Celeste L. Pearce
Ellen L. Goode
Joellen M. Schildkraut
Kirsten B. Moysich
Laufey T. Amundadottir
Eric J. Jacobs
Alison P. Klein
Gloria M. Petersen
Harvey A. Risch
Rachel Z. Stolzenberg-Solomon
Brian M. Wolpin
Donghui Li
Rosalind A. Eeles
Christopher A. Haiman
Zsofia Kote-Jarai
Fredrick R. Schumacher
Ali Amin Al Olama
Mark P. Purdue
Ghislaine Scelo
Marlene D. Dalgaard
Mark H. Greene
Tom Grotmol
Peter A. Kanetsky
Katherine A. McGlynn
Katherine L. Nathanson
Clare Turnbull
Fredrik Wiklund
Breast Cancer Association Consortium (BCAC)
Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON)
Colon Cancer Family Registry (CCFR)
Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (CORECT)
Endometrial Cancer Association Consortium (ECAC)
Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO)
Melanoma Genetics Consortium (GenoMEL)
Glioma International Case-Control Study (GICC)
International Lung Cancer Consortium (ILCCO)
Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium
International Consortium of Investigators Working on Non-Hodgkin’s Lymphoma Epidemiologic Studies (InterLymph)
Ovarian Cancer Association Consortium (OCAC)
Oral Cancer GWAS
Pancreatic Cancer Case-Control Consortium (PanC4)
Pancreatic Cancer Cohort Consortium (PanScan)
Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL)
Renal Cancer GWAS
Testicular Cancer Consortium (TECAC)
Stephen J. Chanock
Nilanjan Chatterjee
Montserrat Garcia-Closas
Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
Nature Communications
author_facet Yan Dora Zhang
Amber N. Hurson
Haoyu Zhang
Parichoy Pal Choudhury
Douglas F. Easton
Roger L. Milne
Jacques Simard
Per Hall
Kyriaki Michailidou
Joe Dennis
Marjanka K. Schmidt
Jenny Chang-Claude
Puya Gharahkhani
David Whiteman
Peter T. Campbell
Michael Hoffmeister
Mark Jenkins
Ulrike Peters
Li Hsu
Stephen B. Gruber
Graham Casey
Stephanie L. Schmit
Tracy A. O’Mara
Amanda B. Spurdle
Deborah J. Thompson
Ian Tomlinson
Immaculata De Vivo
Maria Teresa Landi
Matthew H. Law
Mark M. Iles
Florence Demenais
Rajiv Kumar
Stuart MacGregor
D. Timothy Bishop
Sarah V. Ward
Melissa L. Bondy
Richard Houlston
John K. Wiencke
Beatrice Melin
Jill Barnholtz-Sloan
Ben Kinnersley
Margaret R. Wrensch
Christopher I. Amos
Rayjean J. Hung
Paul Brennan
James McKay
Neil E. Caporaso
Sonja I. Berndt
Brenda M. Birmann
Nicola J. Camp
Peter Kraft
Nathaniel Rothman
Susan L. Slager
Andrew Berchuck
Paul D. P. Pharoah
Thomas A. Sellers
Simon A. Gayther
Celeste L. Pearce
Ellen L. Goode
Joellen M. Schildkraut
Kirsten B. Moysich
Laufey T. Amundadottir
Eric J. Jacobs
Alison P. Klein
Gloria M. Petersen
Harvey A. Risch
Rachel Z. Stolzenberg-Solomon
Brian M. Wolpin
Donghui Li
Rosalind A. Eeles
Christopher A. Haiman
Zsofia Kote-Jarai
Fredrick R. Schumacher
Ali Amin Al Olama
Mark P. Purdue
Ghislaine Scelo
Marlene D. Dalgaard
Mark H. Greene
Tom Grotmol
Peter A. Kanetsky
Katherine A. McGlynn
Katherine L. Nathanson
Clare Turnbull
Fredrik Wiklund
Breast Cancer Association Consortium (BCAC)
Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON)
Colon Cancer Family Registry (CCFR)
Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (CORECT)
Endometrial Cancer Association Consortium (ECAC)
Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO)
Melanoma Genetics Consortium (GenoMEL)
Glioma International Case-Control Study (GICC)
International Lung Cancer Consortium (ILCCO)
Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium
International Consortium of Investigators Working on Non-Hodgkin’s Lymphoma Epidemiologic Studies (InterLymph)
Ovarian Cancer Association Consortium (OCAC)
Oral Cancer GWAS
Pancreatic Cancer Case-Control Consortium (PanC4)
Pancreatic Cancer Cohort Consortium (PanScan)
Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL)
Renal Cancer GWAS
Testicular Cancer Consortium (TECAC)
Stephen J. Chanock
Nilanjan Chatterjee
Montserrat Garcia-Closas
author_sort Yan Dora Zhang
title Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
title_short Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
title_full Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
title_fullStr Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
title_full_unstemmed Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
title_sort assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
publisher Nature Publishing Group
series Nature Communications
issn 2041-1723
publishDate 2020-07-01
description In cancer many gene variants may contribute to disease etiology, but the impact of a given gene variant may have varied effect size. Here, the authors analyse summary statistics of genome-wide association studies from fourteen cancers, and show the utility of polygenic risk scores may vary depending on cancer type.
url https://doi.org/10.1038/s41467-020-16483-3
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spelling doaj-043bfd656ef148a0993f50953c04b25f2021-07-04T11:47:07ZengNature Publishing GroupNature Communications2041-17232020-07-0111111310.1038/s41467-020-16483-3Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancersYan Dora Zhang0Amber N. Hurson1Haoyu Zhang2Parichoy Pal Choudhury3Douglas F. Easton4Roger L. Milne5Jacques Simard6Per Hall7Kyriaki Michailidou8Joe Dennis9Marjanka K. Schmidt10Jenny Chang-Claude11Puya Gharahkhani12David Whiteman13Peter T. Campbell14Michael Hoffmeister15Mark Jenkins16Ulrike Peters17Li Hsu18Stephen B. Gruber19Graham Casey20Stephanie L. Schmit21Tracy A. O’Mara22Amanda B. Spurdle23Deborah J. Thompson24Ian Tomlinson25Immaculata De Vivo26Maria Teresa Landi27Matthew H. Law28Mark M. Iles29Florence Demenais30Rajiv Kumar31Stuart MacGregor32D. Timothy Bishop33Sarah V. Ward34Melissa L. Bondy35Richard Houlston36John K. Wiencke37Beatrice Melin38Jill Barnholtz-Sloan39Ben Kinnersley40Margaret R. Wrensch41Christopher I. Amos42Rayjean J. Hung43Paul Brennan44James McKay45Neil E. Caporaso46Sonja I. Berndt47Brenda M. Birmann48Nicola J. Camp49Peter Kraft50Nathaniel Rothman51Susan L. Slager52Andrew Berchuck53Paul D. P. Pharoah54Thomas A. Sellers55Simon A. Gayther56Celeste L. Pearce57Ellen L. Goode58Joellen M. Schildkraut59Kirsten B. Moysich60Laufey T. Amundadottir61Eric J. Jacobs62Alison P. Klein63Gloria M. Petersen64Harvey A. Risch65Rachel Z. Stolzenberg-Solomon66Brian M. Wolpin67Donghui Li68Rosalind A. Eeles69Christopher A. Haiman70Zsofia Kote-Jarai71Fredrick R. Schumacher72Ali Amin Al Olama73Mark P. Purdue74Ghislaine Scelo75Marlene D. Dalgaard76Mark H. Greene77Tom Grotmol78Peter A. Kanetsky79Katherine A. McGlynn80Katherine L. Nathanson81Clare Turnbull82Fredrik Wiklund83Breast Cancer Association Consortium (BCAC)Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON)Colon Cancer Family Registry (CCFR)Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (CORECT)Endometrial Cancer Association Consortium (ECAC)Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO)Melanoma Genetics Consortium (GenoMEL)Glioma International Case-Control Study (GICC)International Lung Cancer Consortium (ILCCO)Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) ConsortiumInternational Consortium of Investigators Working on Non-Hodgkin’s Lymphoma Epidemiologic Studies (InterLymph)Ovarian Cancer Association Consortium (OCAC)Oral Cancer GWASPancreatic Cancer Case-Control Consortium (PanC4)Pancreatic Cancer Cohort Consortium (PanScan)Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL)Renal Cancer GWASTesticular Cancer Consortium (TECAC)Stephen J. Chanock84Nilanjan Chatterjee85Montserrat Garcia-Closas86Department of Statistics and Actuarial Science, Faculty of Science, The University of Hong KongDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Oncology, Centre for Cancer Genetic Epidemiology, University of CambridgeCancer Epidemiology Division, Cancer Council VictoriaCentre Hospitalier Universitaire de Québec–Université Laval Research CenterDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of CambridgeDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of CambridgeDivision of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek HospitalDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ)Statistical Genetics, QIMR Berghofer Medical Research InstituteCancer Control, QIMR Berghofer Medical Research InstituteBehavioral and Epidemiology Research Group, American Cancer SocietyDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of MelbournePublic Health Sciences Division, Fred Hutchinson Cancer Research CenterPublic Health Sciences Division, Fred Hutchinson Cancer Research CenterDepartment of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern CaliforniaDepartment of Public Health Sciences, Center for Public Health Genomics, University of VirginiaDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research InstitutionGenetics and Computational Biology Division, QIMR Berghofer Medical Research InstituteGenetics and Computational Biology Division, QIMR Berghofer Medical Research InstituteDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of CambridgeInstitute of Cancer and Genomic Sciences, University of BirminghamChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolDivision of Cancer Epidemiology and Genetics, National Cancer InstituteStatistical Genetics, QIMR Berghofer Medical Research InstituteSection of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of LeedsUniversité de Paris, UMRS-1124, Institut National de la Santé et de la Recherche Médicale (INSERM)Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ)Statistical Genetics, QIMR Berghofer Medical Research InstituteDivision of Haematology and Immunology, Leeds Institute of Medical Research, University of LeedsCentre for Genetic Origins of Health and Disease, School of Biomedical Sciences, The University of Western AustraliaDepartment of Medicine, Section of Epidemiology and Population Sciences, Baylor College of MedicineDivision of Genetics and Epidemiology, The Institute of Cancer ResearchDepartment of Neurological Surgery, School of Medicine, University of California, San FranciscoDepartment of Radiation Sciences Oncology, Umeå UniversityCase Comprehensive Cancer Center, Case Western Reserve University School of MedicineDivision of Genetics and Epidemiology, The Institute of Cancer ResearchDepartment of Neurological Surgery, School of Medicine, University of California, San FranciscoInstitute for Clinical and Translational Research, Dan L. Duncan Comprehensive Cancer Center, Baylor College of MedicineLunenfeld-Tanenbuaum Research Institute, Sinai Health SystemInternational Agency for Research on Cancer, World Health OrganizationInternational Agency for Research on Cancer, World Health OrganizationDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolDivision of Hematology and Hematological Malignancies, University of Utah School of MedicineProgram in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public HealthDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Biomedical Statistics & Informatics, Department of Health Sciences Research, Mayo ClinicDepartment of Gynecologic Oncology, Duke University Medical CenterDepartment of Oncology, Centre for Cancer Genetic Epidemiology, University of CambridgeDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research InstitutionCenter for Bioinformatics and Functional Genomics and the Cedars Sinai Genomics Core, Cedars-Sinai Medical CenterDepartment of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern CaliforniaDivision of Epidemiology, Department of Health Science Research, Mayo ClinicRollins School of Public Health, Emory UniversityDivision of Cancer Prevention and Control, Roswell Park Cancer InstituteLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of HealthBehavioral and Epidemiology Research Group, American Cancer SocietyDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of MedicineDivision of Epidemiology, Department of Health Science Research, Mayo ClinicChronic Disease Epidemiology, Yale School of MedicineDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDivision of Cancer Medicine, GI Medical Oncology Department, The University of Texas MD Anderson Cancer CenterDivision of Genetics and Epidemiology, The Institute of Cancer ResearchDepartment of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern CaliforniaDivision of Genetics and Epidemiology, The Institute of Cancer ResearchDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of MedicineStrangeways Research Laboratory, Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of CambridgeDivision of Cancer Epidemiology and Genetics, National Cancer InstituteInternational Agency for Research on Cancer, World Health OrganizationDepartment of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet)Clinical Genetics Branch, Division of Cancer Genetics and Epidemiology, National Cancer InstituteCancer Registry of NorwayDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research InstitutionDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Translational Health and Human Genetics, Department of Medicine, University of PennsylvaniaDivision of Genetics and Epidemiology, The Institute of Cancer ResearchDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins UniversityDivision of Cancer Epidemiology and Genetics, National Cancer InstituteIn cancer many gene variants may contribute to disease etiology, but the impact of a given gene variant may have varied effect size. Here, the authors analyse summary statistics of genome-wide association studies from fourteen cancers, and show the utility of polygenic risk scores may vary depending on cancer type.https://doi.org/10.1038/s41467-020-16483-3