PRState: Incorporating Genetic Ancestry in Prostate Cancer Risk scores for African American Men
Pagadala, M.; Linscott, J. A.; Talwar, J.; Seibert, T.; Rose, B.; Lynch, J.; Panizzon, M. S.; Hauger, R.; Hansen, M. H.; Sammon, J. D.; Hayn, M. H.; Kader, K.; Carter, H. K.; Ryan, S. T.
Show abstract
Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. African American men are at an increased risk of PrCa; however, current risk prediction models are based on European ancestry groups and may not be broadly applicable. In this study, we define an African ancestry group of 4,533 individuals to develop an African ancestry-specific PrCa polygenic risk score (PRState). We identified risk loci on chromosomes 3, 8, and 11 in the African ancestry group GWAS and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60-0.63] and 0.65 [0.64-0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program, demonstrating improved prediction of PrCa and metastatic PrCa in African American individuals. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRS.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry 97%
- Validation and context-dependent effects of a prostate cancer polygenic risk score in the All of Us Research Program 92%
- A joint transcriptome-wide association study across multiple tissues identifies new candidate susceptibility genes for breast cancer 92%
Similar papers in this journal
- Non-coding genetic variants underlying higher prostate cancer risk in men of African ancestry 94%
- The genomic landscape of metastatic castration-resistant prostate cancers reveals multiple distinct genotypes with potential clinical impact 93%
- Role of Specialized mSWI/SNF Complexes in Prostate Cancer Lineage Plasticity 93%
Similar papers in this journal
- A new colorectal cancer risk prediction model incorporating family history, personal and environmental factors 92%
- Hereditary haemochromatosis beyond liver cancer: increased risk of prostate cancer during an 11-year follow-up 91%
- The Multiethnic Cohort: A Resource for the study of Genetic and non-Genetic Cancer Risk Across Populations 90%
Similar papers in this journal
Similar papers in this journal
- Genetic Factors Associated with Prostate Cancer Conversion from Active Surveillance to Treatment 96%
- Investigating the Role of Neighborhood Socioeconomic Status and Germline Genetics on Prostate Cancer Risk 92%
- Evaluating Genomic Polygenic Risk Scores for Childhood Acute Lymphoblastic Leukemia in Latinos 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.