TY - JOUR
T1 - Genetic ancestry in population pharmacogenomics unravels distinct geographical patterns related to drug toxicity
AU - Karamperis, Kariofyllis
AU - Katz, Sonja
AU - Melograna, Federico
AU - Ganau, Francesc P.
AU - Van Steen, Kristel
AU - Patrinos, George P.
AU - Lao, Oscar
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/10/18
Y1 - 2024/10/18
N2 - Genetic ancestry plays a major role in pharmacogenomics, and a deeper understanding of the genetic diversity among individuals holds immerse promise for reshaping personalized medicine. In this pivotal study, we have conducted a large-scale genomic analysis of 1,136 pharmacogenomic variants employing machine learning algorithms on 3,714 individuals from publicly available datasets to assess the risk proximity of experiencing drug-related adverse events. Our findings indicate that Admixed Americans and Europeans have demonstrated a higher risk of experiencing drug toxicity, whereas individuals with East Asian ancestry and, to a lesser extent, Oceanians displayed a lower risk proximity. Polygenic risk scores for drug-gene interactions did not necessarily follow similar assumptions, reflecting distinct genetic patterns and population-specific differences that vary depending on the drug class. Overall, our results provide evidence that genetic ancestry is a pivotal factor in population pharmacogenomics and should be further exploited to strengthen even more personalized drug therapy.
AB - Genetic ancestry plays a major role in pharmacogenomics, and a deeper understanding of the genetic diversity among individuals holds immerse promise for reshaping personalized medicine. In this pivotal study, we have conducted a large-scale genomic analysis of 1,136 pharmacogenomic variants employing machine learning algorithms on 3,714 individuals from publicly available datasets to assess the risk proximity of experiencing drug-related adverse events. Our findings indicate that Admixed Americans and Europeans have demonstrated a higher risk of experiencing drug toxicity, whereas individuals with East Asian ancestry and, to a lesser extent, Oceanians displayed a lower risk proximity. Polygenic risk scores for drug-gene interactions did not necessarily follow similar assumptions, reflecting distinct genetic patterns and population-specific differences that vary depending on the drug class. Overall, our results provide evidence that genetic ancestry is a pivotal factor in population pharmacogenomics and should be further exploited to strengthen even more personalized drug therapy.
UR - http://www.scopus.com/inward/record.url?scp=85207351426&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2024.110916
DO - 10.1016/j.isci.2024.110916
M3 - Article
C2 - 39391720
AN - SCOPUS:85207351426
VL - 27
JO - iScience
JF - iScience
IS - 10
M1 - 110916
ER -