Yiangou Kristia, Mavaddat Nasim, Dennis Joe, Zanti Maria, Wang Qin, Bolla Manjeet K, Abubakar Mustapha, Ahearn Thomas U, Andrulis Irene L, Anton-Culver Hoda, Antonenkova Natalia N, Arndt Volker, Aronson Kristan J, Augustinsson Annelie, Baten Adinda, Behrens Sabine, Bermisheva Marina, de Gonzalez Amy Berrington, Białkowska Katarzyna, Boddicker Nicholas, Bodelon Clara, Bogdanova Natalia V, Bojesen Stig E, Brantley Kristen D, Brauch Hiltrud, Brenner Hermann, Camp Nicola J, Canzian Federico, Castelao Jose E, Cessna Melissa H, Chang-Claude Jenny, Chenevix-Trench Georgia, Chung Wendy K, Colonna Sarah V, Couch Fergus J, Cox Angela, Cross Simon S, Czene Kamila, Daly Mary B, Devilee Peter, Dörk Thilo, Dunning Alison M, Eccles Diana M, Eliassen A Heather, Engel Christoph, Eriksson Mikael, Evans D Gareth, Fasching Peter A, Fletcher Olivia, Flyger Henrik, Fritschi Lin, Gago-Dominguez Manuela, Gentry-Maharaj Aleksandra, González-Neira Anna, Guénel Pascal, Hahnen Eric, Haiman Christopher A, Hamann Ute, Hartikainen Jaana M, Ho Vikki, Hodge James, Hollestelle Antoinette, Honisch Ellen, Hooning Maartje J, Hoppe Reiner, Hopper John L, Howell Sacha, Howell Anthony, Jakovchevska Simona, Jakubowska Anna, Jernström Helena, Johnson Nichola, Kaaks Rudolf, Khusnutdinova Elza K, Kitahara Cari M, Koutros Stella, Kristensen Vessela N, Lacey James V, Lambrechts Diether, Lejbkowicz Flavio, Lindblom Annika, Lush Michael, Mannermaa Arto, Mavroudis Dimitrios, Menon Usha, Murphy Rachel A, Nevanlinna Heli, Obi Nadia, Offit Kenneth, Park-Simon Tjoung-Won, Patel Alpa V, Peng Cheng, Peterlongo Paolo, Pita Guillermo, Plaseska-Karanfilska Dijana, Pylkäs Katri, Radice Paolo, Rashid Muhammad U, Rennert Gad, Roberts Eleanor, Rodriguez Juan, Romero Atocha, Rosenberg Efraim H, Saloustros Emmanouil, Sandler Dale P, Sawyer Elinor J, Schmutzler Rita K, Scott Christopher G, Shu Xiao-Ou, Southey Melissa C, Stone Jennifer, Taylor Jack A, Teras Lauren R, van de Beek Irma, Willett Walter, Winqvist Robert, Zheng Wei, Vachon Celine M, Schmidt Marjanka K, Hall Per, MacInnis Robert J, Milne Roger L, Pharoah Paul D P, Simard Jacques, Antoniou Antonis C, Easton Douglas F, Michailidou Kyriaki
Biostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus, 2371.
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK, CB1 8RN.
medRxiv. 2024 Feb 13:2024.02.12.24302043. doi: 10.1101/2024.02.12.24302043.
The 313-variant polygenic risk score (PRS) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS 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 PRS differed markedly across European countries, being highest in south-eastern Europe and lowest in north-western Europe. Using the overall European PRS 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.
313 变体多基因风险评分（PRS）为乳腺癌风险预测提供了一个很有前景的工具。然而，尚未对可能影响风险估计的不同欧洲人群的PRS进行评估。在此，我们利用来自参与乳腺癌协会联盟（BCAC）的21个国家的94072名无乳腺癌的欧洲血统女性的基因型数据，以及来自英国生物银行的225105名女性参与者的数据，探索了欧洲人群中PRS的分布情况。欧洲各国的平均PRS差异显著，在东南欧最高，在西北欧最低。使用整个欧洲的PRS分布对个体进行分类，分别会导致高估东南欧一些个体的风险和低估西北欧一些个体的风险。对主成分进行调整可以解释观察到的平均PRS中大部分的异质性。特定国家的PRS分布可用于校准来自不同国家个体的风险类别。
