we here propose the Genome of Europe project that brings 26 European countries together to establish a Genome of Europe (GoE) reference database of genomes from at least 500,000 citizens. This proposal, represents a detailed outline of the first major step to contribute 100,000 genomes to these overall GoE and 1+MG ambitions. The rationale behind the GoE reference database is to build a comprehensive collection of subgroup-specific reference datasets, serving as the foundation of 'normal' or European reference genomes. The GoE datasets will play a crucial role across several key areas in health care and prevention. In the short term; 1) GoE will enable the documentation and quantification of genetic diversity and heterogeneity across European populations, thus facilitating the interpretation of pathogenic and/or clinically relevant (e.g., pharmacogenomic) variants, 2) the GoE datasets will be instrumental in recalibrating genetic risk profiles based on ancestral backgrounds, an essential step in the development of accurate polygenic risk scores, and 3) the GoE cohort will serve as a reference panel for imputations in large-scale array genotyping efforts, particularly for those projects focused on lower resolution but broader population studies. In the longer term; 1) GoE will aid in novel discovery of genetic-phenotypic associations by linking to clinical phenotypes, and 2) (re-)usability of the GoE will serve as a reference for genomic health programs across European countries, fostering advancements in personalized medicine and population-wide health initiatives. During the 42 months of this proposal, use cases of all three short term applications will be piloted, and future outlines for all applications are considered and planned for.