Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry

Burcu F. Darst; Jiayi Shen; Ravi K. Madduri; Alexis A. Rodriguez; Yukai Xiao; Xin Sheng; Edward J. Saunders; Tokhir Dadaev; Mark N. Brook; Thomas J. Hoffmann; Kenneth Muir; Peggy Wan; Loic Le Marchand; Lynne Wilkens; Ying Wang; Johanna Schleutker; Robert J. MacInnis; Cezary Cybulski; David E. Neal; Børge G. Nordestgaard; Sune F. Nielsen; Jyotsna Batra; Judith A. Clements; Australian Prostate Cancer BioResource; Henrik Grönberg; Nora Pashayan; Ruth C. Travis; Jong Y. Park; Demetrius Albanes; Stephanie Weinstein; Lorelei A. Mucci; David J. Hunter; Kathryn L. Penney; Catherine M. Tangen; Robert J. Hamilton; Marie-Élise Parent; Janet L. Stanford; Stella Koutros; Alicja Wolk; Karina D. Sørensen; William J. Blot; Edward D. Yeboah; James E. Mensah; Yong-Jie Lu; Daniel J. Schaid; Stephen N. Thibodeau; Catharine M. West; Christiane Maier; Adam S. Kibel; Géraldine Cancel-Tassin; Florence Menegaux; Esther M. John; Eli Marie Grindedal; Kay-Tee Khaw; Sue A. Ingles; Ana Vega; Barry S. Rosenstein; Manuel R. Teixeira; Manolis Kogevinas; Lisa Cannon-Albright; Chad Huff; Luc Multigner; Radka Kaneva; Robin J. Leach; Hermann Brenner; Ann W. Hsing; Rick A. Kittles; Adam B. Murphy; Christopher J. Logothetis; Susan L. Neuhausen; William B. Isaacs; Barbara Nemesure; Anselm J. Hennis; John Carpten; Hardev Pandha; Kim De Ruyck; Jianfeng Xu; Azad Razack; Soo-Hwang Teo; Lisa F. Newcomb; Jay H. Fowke; Christine Neslund-Dudas; Benjamin A. Rybicki; Marija Gamulin; Nawaid Usmani; Frank Claessens; Manuela Gago-Dominguez; Jose Esteban Castelao; Paul A. Townsend; Dana C. Crawford; Gyorgy Petrovics; Graham Casey; Monique J. Roobol; Jennifer F. Hu; Sonja I. Berndt; Stephen K. Van Den Eeden; Douglas F. Easton; Stephen J. Chanock; Michael B. Cook; Fredrik Wiklund; John S. Witte; Rosalind A. Eeles; Zsofia Kote-Jarai; Stephen Watya; John M. Gaziano; Amy C. Justice; David V. Conti; Christopher A. Haiman; Canary PASS Investigators

doi:10.1016/j.ajhg.2023.05.010

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Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry

Journal article

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Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry

Burcu F. Darst, Jiayi Shen, Ravi K. Madduri, Alexis A. Rodriguez, Yukai Xiao, Xin Sheng, Edward J. Saunders, Tokhir Dadaev, Mark N. Brook, Thomas J. Hoffmann, …

American journal of human genetics, Vol.110(7), pp.1200-1206

06/07/2023

DOI: https://doi.org/10.1016/j.ajhg.2023.05.010

PMID: 37311464

Abstract

African ancestry

genome-wide polygenic risk score

health disparities

polygenic risk score

risk modeling

Genetics

Prostate Cancer

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635–0.677) in African and 0.844 (95% CI = 0.840–0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67–2.00) and 2.19 (95% CI = 2.14–2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659–0.700 and AUC = 0.845, 95% CI = 0.841–0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87–2.26 and OR = 2.21, 95% CI = 2.16–2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping. Our findings suggest that in men of African and European ancestry, genome-wide polygenic risk scores including >1 million variants are not more predictive of prostate cancer risk than a carefully constructed polygenic risk score limited to variants with statistical evidence of an association with prostate cancer risk.

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Title: Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry
Creators: Burcu F. Darst - Fred Hutch Cancer Center
Jiayi Shen - University of Southern California
Ravi K. Madduri - Argonne National Laboratory
Alexis A. Rodriguez - Argonne National Laboratory
Yukai Xiao - Argonne National Laboratory
Xin Sheng - University of Southern California
Edward J. Saunders - The Institute of Cancer Research, London, UK
Tokhir Dadaev - Institute of Cancer Research
Mark N. Brook - Institute of Cancer Research
Thomas J. Hoffmann - University of California, San Francisco
Kenneth Muir - Manchester Academic Health Science Centre
Peggy Wan - University of Southern California
Loic Le Marchand - University of Hawaii System
Lynne Wilkens - Cancer Center of Hawaii
Ying Wang - American Cancer Society
Johanna Schleutker - University of Turku
Robert J. MacInnis - University of Melbourne
Cezary Cybulski - Pomeranian Medical University
David E. Neal - Addenbrooke's Hospital
Børge G. Nordestgaard - Gentofte Hospital
Sune F. Nielsen - Gentofte Hospital
Jyotsna Batra - Translational Research Institute
Judith A. Clements - Translational Research Institute
Australian Prostate Cancer BioResource - Translational Research Institute
Henrik Grönberg - Karolinska Institutet
Nora Pashayan - University of Cambridge
Ruth C. Travis - University of Oxford
Jong Y. Park - Moffitt Cancer Center
Demetrius Albanes - National Cancer Institute
Stephanie Weinstein - National Cancer Institute
Lorelei A. Mucci - Harvard University
David J. Hunter - University of Oxford
Kathryn L. Penney - Brigham and Women's Hospital
Catherine M. Tangen - Fred Hutch Cancer Center
Robert J. Hamilton - University of Toronto
Marie-Élise Parent - Institut National de la Recherche Scientifique
Janet L. Stanford - University of Washington
Stella Koutros - National Cancer Institute
Alicja Wolk - Karolinska Institutet
Karina D. Sørensen - Aarhus University Hospital
William J. Blot - Vanderbilt University Medical Center
Edward D. Yeboah - University of Ghana
James E. Mensah - University of Ghana
Yong-Jie Lu - Queen Mary University of London
Daniel J. Schaid - Mayo Clinic in Florida
Stephen N. Thibodeau - Mayo Clinic in Arizona
Catharine M. West - University of Manchester
Christiane Maier - Praxis für Humangenetik Tübingen
Adam S. Kibel - Brigham and Women's Hospital
Géraldine Cancel-Tassin - Hôpital Tenon
Florence Menegaux - Université Paris-Saclay
Esther M. John - Stanford University
Eli Marie Grindedal - Oslo University Hospital
Kay-Tee Khaw - University of Cambridge
Sue A. Ingles - University of Southern California
Ana Vega - Fundación Pública Galega de Medicina Xenómica
Barry S. Rosenstein - Icahn School of Medicine at Mount Sinai
Manuel R. Teixeira - Universidade do Porto
Manolis Kogevinas - Barcelona Institute for Global Health
Lisa Cannon-Albright - George E. Wahlen Department of VA Medical Center
Chad Huff - The University of Texas MD Anderson Cancer Center
Luc Multigner - Institut de Recherche en Santé, Environnement et Travail
Radka Kaneva - Medical University of Sofia
Robin J. Leach - The University of Texas Health Science Center at San Antonio
Hermann Brenner - National Center for Tumor Diseases
Ann W. Hsing - Stanford University
Rick A. Kittles - City of Hope
Adam B. Murphy - Northwestern University
Christopher J. Logothetis - The University of Texas MD Anderson Cancer Center
Susan L. Neuhausen - City of Hope
William B. Isaacs - Johns Hopkins Hospital
Barbara Nemesure - Stony Brook University
Anselm J. Hennis - University of the West Indies
John Carpten - University of Southern California
Hardev Pandha - University of Surrey
Kim De Ruyck - Ghent University
Jianfeng Xu - NorthShore University HealthSystem
Azad Razack - Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
Soo-Hwang Teo - Subang Jaya Medical Centre
Lisa F. Newcomb - University of Washington
Jay H. Fowke - University of Tennessee Health Science Center
Christine Neslund-Dudas - Henry Ford Hospital
Benjamin A. Rybicki - Henry Ford Hospital
Marija Gamulin - University Hospital Centre Zagreb
Nawaid Usmani - University of Alberta
Frank Claessens - Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, Leuven, Belgium
Manuela Gago-Dominguez - University of California, San Diego
Jose Esteban Castelao - Complexo Hospitalario Universitario A Coruña
Paul A. Townsend - University of Manchester
Dana C. Crawford - Case Western Reserve University
Gyorgy Petrovics - Uniformed Services University of the Health Sciences
Graham Casey - University of Virginia
Monique J. Roobol - Erasmus MC Cancer Institute
Jennifer F. Hu - Sylvester Comprehensive Cancer Center
Sonja I. Berndt - National Cancer Institute
Stephen K. Van Den Eeden - Kaiser Permanente
Douglas F. Easton - University of Cambridge
Stephen J. Chanock - National Cancer Institute
Michael B. Cook - National Cancer Institute
Fredrik Wiklund - Karolinska Institutet
John S. Witte - Department of Epidemiology and Population Health, Department of Biomedical Data Science, Stanford Cancer Institute, Stanford, CA, USA
Rosalind A. Eeles - Royal Marsden NHS Foundation Trust
Zsofia Kote-Jarai - The Institute of Cancer Research, Sutton, London, UK
Stephen Watya - Makerere University
John M. Gaziano - VA Boston Healthcare System
Amy C. Justice - VA Connecticut Healthcare System
David V. Conti - University of Southern California
Christopher A. Haiman - University of Southern California
Canary PASS Investigators
Publication Details: American journal of human genetics, Vol.110(7), pp.1200-1206
Publisher: Elsevier Inc
Date published: 06/07/2023
Identifiers: 99820328002346
Academic Unit: Faculty of Health and Medical Sciences; FHMS Central Faculty Admin
Language: English
Resource Type: Journal article
SDG (Scopus 2023): SDG 3| SDG 10

Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry

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