Revisiting Founder Populations in an Age of Global Biobanks

Founder populations have played a pivotal role in human genetics, enabling the discovery of causal variants for disease and providing insight into population history and dynamics. The rapid expansion of global genomic databases has revealed that founder populations are far more common than once recognized, as population-scale sequencing now allows for systematic detection of founder events and founder-like population structure across the world. Contemporary genomic methods facilitate the characterization of founder populations using genetic metrics such as identity by descent, runs of homozygosity, and haplotype-based clustering. As the field shifts from small, ascertained founder cohorts to biobank-scale datasets containing millions of participants, new opportunities and challenges have emerged, including analytical, interpretive, and ethical complexities in the study of founder populations. Here, we review the historical and ongoing contributions of founder populations to genetics, outline current approaches for biobanks, and highlight growing opportunities to integrate founder population research into genomic medicine.