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  5. Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction

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Preprint
en
2024

Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction

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en
2024
DOI: 10.1101/2024.02.12.24302043

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Hermann Brenner
Hermann Brenner

Institution not specified

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Kristia Yiangou
Nasim Mavaddat
Joe Dennis
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Abstract

The 313-variant polygenic risk score (PRS313) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS313 across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS313 across European populations using genotype data from 94,072 females without breast cancer, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 225,105 female participants from the UK Biobank. The mean PRS313 differed markedly across European countries, being highest in south-eastern Europe and lowest in north-western Europe. Using the overall European PRS313 distribution to categorise individuals leads to overestimation and underestimation of risk in some individuals from south-eastern and north-western countries, respectively. Adjustment for principal components explained most of the observed heterogeneity in mean PRS. Country-specific PRS distributions may be used to calibrate risk categories in individuals from different countries.

How to cite this publication

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 Antonenkova, Volker Arndt, Kristan J. Aronson, Annelie Augustinsson, Adinda Baten, Sabine Behrens, Marina Bermisheva, Amy Berrington de González, Katarzyna Białkowska, Nicholas Boddicker, Clara Bodelón, Natalia 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 Eccles, A. Heather Eliassen, Christoph Engel, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Olivia Fletcher, Henrik Flyger, Lin Fritschi, Manuela Gago-Domínguez, Aleksandra Gentry‐Maharaj, Anna González‐Neira, Pascal Guénel, Eric Hahnen, Christopher A. Haiman, Ute Hamann, Jaana M. Hartikainen, Vikki Ho, James M. Hodge, Antoinette Hollestelle, Ellen Honisch, Maartje J. Hooning, Reiner Hoppe, John L. Hopper, Sacha J. Howell, Anthony Howell, Simona Jakovchevska, Anna Jakubowska, Helena Jernström, Nichola Johnson, Rudolf Kaaks, Э. К. Хуснутдинова, 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 (2024). Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction. , DOI: https://doi.org/10.1101/2024.02.12.24302043.

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Publication Details

Type

Preprint

Year

2024

Authors

97

Datasets

0

Total Files

0

Language

en

DOI

https://doi.org/10.1101/2024.02.12.24302043

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