Human genomics in Europe: from national and pan-European initiatives to genomic medicine

Abstract Advances in high-throughput sequencing technologies have transformed human genomics, enabling large-scale initiatives to characterise genome structure, function, and population diversity. Following foundational international projects such as the Human Genome Project, HapMap, and the 1000 Genomes Project, many countries have developed national sequencing initiatives to generate population-specific genomic resources and support precision medicine. In this review, we examine the development of human genomic sequencing initiatives with a particular focus on Europe, where national projects differ substantially in their objectives, infrastructure, governance, funding models, cohort design, and degree of integration with healthcare systems. We further consider how pan-European programmes are increasingly linking these heterogeneous national efforts through shared standards, federated data infrastructures, and coordinated population-reference initiatives. Comparisons with selected initiatives from other world regions highlight common challenges, including unequal population representation, long-term sustainability, data governance, interoperability, and translation into clinical practice. We also discuss the growing impact of long-read sequencing and artificial intelligence on population genomics and genomic medicine. Overall, the European landscape illustrates that successful genomic initiatives depend not simply on sequencing scale, but on the alignment of scientific objectives with representative recruitment, sustainable infrastructure and financing, interoperable data systems, and pathways for clinical implementation.