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Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations
Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States.
Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Biostatistics Division, Kaiser Permanente Washington Health Research Institute, Seattle, United States.
Department of Medicine (Medical Genetics), University of Washington Medical Center, WA, Seattle, United States.
Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States.
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2023 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1, article id 6147Article in journal (Refereed) Published
Abstract [en]

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.

Place, publisher, year, edition, pages
Springer Nature, 2023. Vol. 14, no 1, article id 6147
National Category
Medical Genetics and Genomics
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URN: urn:nbn:se:umu:diva-216170DOI: 10.1038/s41467-023-41819-0ISI: 001084354900002Scopus ID: 2-s2.0-85173730049OAI: oai:DiVA.org:umu-216170DiVA, id: diva2:1811058
Available from: 2023-11-10 Created: 2023-11-10 Last updated: 2025-04-24Bibliographically approved

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van Guelpen, Bethany

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