Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations.

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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.


Acknowledgements: National Cancer Institute, National Human Genome Research Institute (R01 CA244588 (Ulrike Peters), U01 CA164930 (Ulrike Peters), U01 CA137088 (Ulrike Peters), R01 CA059045 (Ulrike Peters), R01 CA201407 (Ulrike Peters), R01 CA206279 (Ulrike Peters), U01 CA261339 (David V Conti), R01 CA185094 (Ulrike Peters), U01 HG008657 (Gail P. Jarvik)).

Funder: NHGRI U01HG008657 (Gail Jarvik) NCI R01CA244588 (Ulrike Peters) NCI U01 CA137088 (Ulrike Peters) NCI R01 CA059045 (Ulrike Peters) NCI R01 CA201407 (Ulrike Peters) NCI R01CA206279 (Ulrike Peters) NCI U01CA261339 (David Conti) NCI U01 CA164930 (Ulrike Peters) NCI R01 CA185094 (Ulrike Peters)

Humans, Ethnicity, Genome-Wide Association Study, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Risk Factors, Multifactorial Inheritance, Colorectal Neoplasms
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