Disparity in genomic application
Although PRS predictive power is high, PRS studies suffer from a
significant deficit in the inclusion of African Americans, which
represent only around 3% of the participants for GWASs published
through 2015 32 33. The insufficient
inclusion of African Americans leads to a disproportion in identifying
risk-associated SNPs and compromises the predictive potential of PRS
over this minority group19. As a result, there might
be an imbalance in how PRS can improve care for patients of European
descent versus patients of African descent32. In a
multi-ethnic study of 80,481 participants, prostate cancer PRS
performance was superior in those with genetically defined European
ancestry than in those with African ancestry, which comprised 89.3% and
7.8% of the study population respectively28. This
disparity is inevitable considering the bias introduced in
European-dominated GWAS28 34. Known
health disparity might also contribute to the diminished predictive
power of PRS in minority groups. For instance, limited healthcare access
leads to missing diagnosis information and failure of early detection of
PCa, paving way for systemic differences in age of diagnosis across
different ethnic groups and leading to inequitable risk
stratification28 34.
A recent trans-ancestry GWAS of 127,006 controls and 107,247 prostate
cancer cases discovered 86 new risk variants, totaling the known risk
variants to 26919. In this study, PRS is shown to have
a larger contribution to overall PCa risk for AAM because variants with
odds ration >1.10, which have a greater effect on PRS, are
more common in African American participants. Notwithstanding, AAM also
have mean PRS that are approximately 2.18 times higher than that of
EAM19. These findings are consistent with the
conclusion that known risk variants substantially accounted for the
estimated 75% higher prostate cancer incidence in African Americans
when compared to non-Hispanic white35.
There has been considerable effort to attenuate the disparity presented
in PRS studies. To compensate for the lack of diversity in GWASs, a
study scaled ancestry-specific PRS distributions that, when considered
separately in each ethnic group, can help identify individuals with
higher PCa risk in each group36. Another study
conducted a cross-validated search on a dataset that comprised only men
with African genetic ancestry and identified three SNPs that
significantly improved the performance of PRS in the studied
population37. While more efforts are underway to
improve diversity in the field of GWAS and improve PRS performance in
minority groups, substantial gaps remain in our understanding.