African‐specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer
Abstract
Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross‐validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10‐fold cross‐validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross‐validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47‐4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65‐0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 24, 2020
- Source ID
- 10.1002/ijc.33282
Entities
People
- Adam S. Kibel
- Anders M. Dale
- Artitaya Lophatananon
- Bettina F. Drake
- Catherine M. Tangen
- Chun C. Fan
- Dana C. Crawford
- Elizabeth T. H. Fontham
- Esther M. John
- Florence Menegaux
- Gyorgy Petrovics
- Géraldine Cancel‐tassin
- Hui‐yi Lin
- Ian G Mills
- Ian M. Thompson, Jr.
- Jack A. Taylor
- James L Mohler
- Jay Fowke
- Jeannette T. Bensen
- Jennifer C. Cullen
- Jennifer J. Hu
- Jong Y Park
- Kenneth Muir
- Laurent Brureau
- Luc Multigner
- Marc Romana
- Marie-Élise Parent
- Maureen Sanderson
- Melinda C. Aldrich
- Minh-Phuong Huynh-Le
- Ole A. Andreassen
- Olivier Cussenot
- Pascal Blanchet
- Phyllis J. Goodman
- Robin J Leach
- Rosalind Eeles
- Roshan A Karunamuni
- Shiv Srivastava
- The Practical Consortium
- Thérèse Truong
- Tyler M Seibert
- Ukgpcs Collaborators
- Wei Zheng
- Wesley Thompson
- William J. Blot
- William S. Bush
- Zsofia Kote‐jarai
Organizations
- Brigham and Women's Hospital
- Case Western Reserve University
- Christus Santa Rosa health system
- H. Lee Moffitt Cancer Center & Research Institute
- Institute of Cancer Research
- Louisiana State University
- Meharry Medical College
- National Institute of Biomedical Imaging and Bioengineering
- National Institute of Environmental Health Sciences
- Paris-Saclay University
- Queen's University Belfast
- Research Council of Norway
- Roswell Park Comprehensive Cancer Center
- Sorbonne University
- Stanford University
- The Royal Marsden NHS Foundation Trust
- Uniformed Services University of the Health Sciences
- United States Department of Defense
- University of California, San Diego
- University of Manchester
- University of Miami
- University of North Carolina at Chapel Hill
- University of Oslo
- University of Tennessee Health Science Center
- University of Warwick
- Université de Montréal
- Vanderbilt University
- Washington University in St. Louis