Using genetic ancestry to improve between-population transferability of a prostate cancer polygenic risk score

Domaine:

healthcare

Type de record:

paper

Créateur:

Sah

Éditeur:

Uni

Hôte:

PSA screening for prostate cancer (PCa) has continuously had the issue of overdiagnosis, especially in minority populations that are more at risk. Polygenic risk scores (PRS) have the potential to ameliorate these deficiencies, but effective methods to translate them to admixed populations are lacking. Several studies have shown that incorporating ancestry proportions can help bridge this gap in translatability. Here, we describe a new method to construct individualized ancestry informed PRS distributions by utilizing reference sets that are representative of a homogeneous sample of superpopulations. Ancestry proportions were estimated using ADMIXTURE in the Multi-Ethnic Cohort (MEC) (N=41,158) using a reference of homogeneous European, African, East Asian, and Amerindian individuals from the 1000 Genomes Project and PAGE Global Reference Panel (N=1,890). A multi-ancestry PCa PRS was calculated in MEC men (N=18,362) and reference individuals, and reference PRS distributions were calculated for each reference superpopulation. For each MEC participant, individualized PRS distributions were calculated as a weighted sum of the reference PRS distributions, utilizing ancestry proportions as weights, and these individualized PRS distributions were used to categorize participants into PRS categories. The PRS was evaluated using logistic regression models, and odds ratios demonstrated an improvement in predictive ability of our new method across diverse populations compared to the standard PRS categorization based on controls of the same sample. Improvement in risk estimates is concurrent with other attempts to incorporate ancestry into PRS construction

Visit

doi.org digitallibrary.usc.edu

Similaires

Supplementary Table 12 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African AncestrySupplementary Table 14 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African AncestrySupplementary Table 20 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African AncestrySupplementary Table 10 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African AncestrySupplementary Table 17 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African AncestrySupplementary Table 15 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry

Supplementary Table 12 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry

Aggregate effect of PRS and P/LP/D variants in BRCA2, ATM, NBN, and PALB2 on PCa risk in African

Supplementary Table 14 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry

Association of PRS and PCa risk in Ugandan men.

Supplementary Table 20 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry

Absolute risk of PCa by PRS and P/LP/D variants in BRCA2, ATM, NBN, and PALB2 combined in African

Supplementary Table 10 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry

Aggregate effect of P/LP/D carrier status across BRCA2, ATM, NBN, and PALB2 genes on PCa risk in

Supplementary Table 17 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry

Aggregate effect of PRS and P/LP/D variants in BRCA1, RAD50, MLH1, and MSH6 on PCa risk in Africa

Supplementary Table 15 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry

Aggregate effect of PRS and P/LP/D variants in BRCA2, ATM, NBN, and PALB2 on PCa risk in Ugandan