Abstract

Polygenic risk scores (PRS) are emerging tools in genomic medicine that estimate an individual’s genetic 
susceptibility to complex diseases by aggregating the effects of multiple genetic variants. While PRS hold promise 
for advancing precision medicine, their application in Indigenous communities raises significant ethical, legal, and 
social concerns. This paper examines the implications of PRS within Indigenous contexts, focusing on informed 
consent, governance frameworks, trust-building, and data sovereignty. It highlights the limitations of PRS derived 
predominantly from European ancestry datasets, which undermine their predictive validity and exacerbate 
existing health inequities for Indigenous populations. The study further explores the importance of culturally 
appropriate consent processes that prioritize collective decision-making and respect Indigenous worldviews. It 
evaluates emerging Indigenous-led governance models and accountability mechanisms designed to safeguard 
community interests and ensure equitable participation in research. Additionally, the paper discusses legal 
considerations surrounding Indigenous data sovereignty, ownership, and cross-border data governance. Despite 
increasing global attention, significant gaps remain in empirical evidence and methodological approaches tailored 
to Indigenous populations. The paper concludes by advocating for inclusive, community-driven research practices, 
strengthened governance structures, and policy reforms that align genomic innovation with Indigenous rights, 
values, and self-determination.