| Title: | Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction |
| Journal: | Breast Cancer Research |
| Published: | 1 Jan 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39734228/ |
| DOI: | https://doi.org/10.1186/s13058-024-01947-x |
Publication 14661
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Abstract
BackgroundThe 313-variant polygenic risk score (PRS313) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS313 across different European populations which could influence risk estimation has not been performed.MethodsWe explored the distribution of PRS313 across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank. The mean PRS was calculated by country in the BCAC dataset and by country of birth in the UK Biobank. We explored different approaches to reduce the observed heterogeneity in the mean PRS across the countries, and investigated the implications of the distribution variability in risk prediction.ResultsThe mean PRS313 differed markedly across European countries, being highest in individuals from Greece and Italy and lowest in individuals from Ireland. Using the overall European PRS313 distribution to define risk categories, leads to overestimation and underestimation of risk in some individuals from these countries. Adjustment for principal components explained most of the observed heterogeneity in the mean PRS. The mean estimates derived when using an empirical Bayes approach were similar to the predicted means after principal component adjustment.ConclusionsOur results demonstrate that PRS distribution differs even within European ancestry populations leading to underestimation or overestimation of risk in specific European countries, which could potentially influence clinical management of some individuals if is not appropriately accounted for. Population-specific PRS distributions may be used in breast cancer risk estimation to ensure predicted risks are correctly calibrated across risk categories.</p>
13 Keywords
- Breast Neoplasms
- Europe
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Genotype
- Humans
- Middle Aged
- Multifactorial Inheritance
- Polymorphism, Single Nucleotide
- Risk Assessment
- Risk Factors
- White People
127 Authors
- Kristia Yiangou
- Nasim Mavaddat
- Joe Dennis
- Maria Zanti
- Qin Wang
- Manjeet K. Bolla
- Mustapha Abubakar
- Thomas U. Ahearn
- Irene L. Andrulis
- Hoda Anton-Culver
- Natalia N. Antonenkova
- Volker Arndt
- Kristan J. Aronson
- Annelie Augustinsson
- Adinda Baten
- Sabine Behrens
- Marina Bermisheva
- Amy Berrington de Gonzalez
- Katarzyna Białkowska
- Nicholas Boddicker
- Clara Bodelon
- Natalia V. Bogdanova
- Stig E. Bojesen
- Kristen D. Brantley
- Hiltrud Brauch
- Hermann Brenner
- Nicola J. Camp
- Federico Canzian
- Jose E. Castelao
- Melissa H. Cessna
- Jenny Chang-Claude
- Georgia Chenevix-Trench
- Wendy K. Chung
- Sarah V. Colonna
- Fergus J. Couch
- Angela Cox
- Simon S. Cross
- Kamila Czene
- Mary B. Daly
- Peter Devilee
- Thilo Dörk
- Alison M. Dunning
- Diana M. Eccles
- A. Heather Eliassen
- Christoph Engel
- Mikael Eriksson
- D. Gareth Evans
- Peter A. Fasching
- Olivia Fletcher
- Henrik Flyger
- Lin Fritschi
- Manuela Gago-Dominguez
- Aleksandra Gentry-Maharaj
- Anna González-Neira
- Pascal Guénel
- Eric Hahnen
- Christopher A. Haiman
- Ute Hamann
- Jaana M. Hartikainen
- Vikki Ho
- James Hodge
- Antoinette Hollestelle
- Ellen Honisch
- Maartje J. Hooning
- Reiner Hoppe
- John L. Hopper
- Sacha Howell
- Anthony Howell
- Simona Jakovchevska
- Anna Jakubowska
- Helena Jernström
- Nichola Johnson
- Rudolf Kaaks
- Elza K. Khusnutdinova
- Cari M. Kitahara
- Stella Koutros
- Vessela N. Kristensen
- James V. Lacey
- Diether Lambrechts
- Flavio Lejbkowicz
- Annika Lindblom
- Michael Lush
- Arto Mannermaa
- Dimitrios Mavroudis
- Usha Menon
- Rachel A. Murphy
- Heli Nevanlinna
- Nadia Obi
- Kenneth Offit
- Tjoung-Won Park-Simon
- Alpa V. Patel
- Cheng Peng
- Paolo Peterlongo
- Guillermo Pita
- Dijana Plaseska-Karanfilska
- Katri Pylkäs
- Paolo Radice
- Muhammad U. Rashid
- Gad Rennert
- Eleanor Roberts
- Juan Rodriguez
- Atocha Romero
- Efraim H. Rosenberg
- Emmanouil Saloustros
- Dale P. Sandler
- Elinor J. Sawyer
- Rita K. Schmutzler
- Christopher G. Scott
- Xiao-Ou Shu
- Melissa C. Southey
- Jennifer Stone
- Jack A. Taylor
- Lauren R. Teras
- Irma van de Beek
- Walter Willett
- Robert Winqvist
- Wei Zheng
- Celine M. Vachon
- Marjanka K. Schmidt
- Per Hall
- Robert J. MacInnis
- Roger L. Milne
- Paul D. P. Pharoah
- Jacques Simard
- Antonis C. Antoniou
- Douglas F. Easton
- Kyriaki Michailidou
1 Application
| Application ID | Title |
|---|---|
| 102655 | Evaluation of rare and common variants in common cancers |
Enabling scientific discoveries that improve human health