André G. Uitterlinden is an emeritus Professor of Complex Genetics and was with > 50 group members head of the Laboratory of Population Genomics and the genomics facility at the Erasmus Medical Centre in Rotterdam. Prof. Uitterlinden has a long standing interest in DNA analysis, both technically as well as applying this to human health related research. He has been mostly involved in identifying genetic factors for common traits and diseases, for which he early on initiated Genome Wide Association Studies (GWAS) in the Netherlands and set up global consortia. In 2005 he initiated a service providing facility which is now, as the genomics Core Facility, one of Europe’s largest genomics facilities, providing services for DNA isolation, genotyping, sequencing, and data analysis, and is handling millions of samples for a global client portfolio. He is now focused on improving the position of Europe in human genomics projects and implementing genetic information in health care and prevention settings. He is PI of the strategic GOALL project within Erasmus MC (“Genotyping On ALL patients”). In 2020 he became member of the coordination team of the European 1+ million genomes initiative, and therein leads the “Genome of Europe” project to establish the first 100,000 reference genomes covering the population diversity across Europe. He has co-authored over 1500 papers (H-index 216)
The Genome of Europe: Towards using Genetic Information in Health Care and Prevention
Most -if not all- human diseases and their risk factors have a genetic component, implying that variance among individuals in susceptibility, treatment response and/or progression, is determined -in part- by genetic variation. DNA analysis technology is developing continuously and allows sequencing a human genome in <24hours (expensive), but also analyzing millions of SNPs in millions of DNA samples using arrays (cheap). Human genome sequencing projects have uncovered hundreds of millions of such genetic variants, but it has been array/chip technology -applied in cohort studies and biobanks- that has identified tens of thousands of genetic factors for common diseases by Genome Wide Association Studies (GWAS).
The 1 million genomes (1+MG) initiative is such a human genome sequencing project and is part of the Digital Europe Program (DEP) and was declared in 2018 by (now) 27 signatory EU countries aiming to make at least 1 million whole genome sequences (WGS) accessible for use in research, health care, and prevention. 1+MG Working Group 12 (WG12) named Genome of Europe (GoE), was started in 2019 with many country representatives to establish a European Reference Genome Database of >500k WGS (@30x coverage). From these discussions a proposal was formulated to sequence the first 100,000 genomes which was awarded for funding by DEP and started in October 2024. With a budget of 45 mio euro GoE has now >30 participating countries, 51 institutes and >300 scientists involved, and has defined a strategy to collect the first 100k genomes to be proportional and representative of the diverse European populations. Production has started with the first national genome collections being finalized, both short read and long read genomes, and the first European T2T genomes. The data collection will adhere to ELSI and ICT guidelines and be made accessible via the Genomics Data Infrastructure (GDI) project which has been previously funded as part of the DEP. Several GoE “use cases” were defined including variant look-ups, genetic diversity analyses, multi-ancestry imputation services, and recalibration of genetic risk profiles, and establish longer term (clinical) applications. GoE will stimulate European genomic research competitiveness, advancing personalized medicine and broader scientific and healthcare objectives and, apart from integrating with European initiatives in health care and prevention, also seek global collaboration with similar genome initiatives.
Altogether, this has led to genetic information now entering the hospital clinic in a broad sense, whereby –in theory- all patients can be assessed for (clinically actionable) DNA mutations and polygenic risk scores, next to pharmacogenomics information and their ancestry, blood groups and HLA profiles, for example. Such genetic information can help clinicians in decision making for diagnosis and treatment, and to provide self-empowerment for patients for prevention. Such a program exploring these opportunities, called GOALL (Genotyping On ALL patients) is running at Erasmus MC in Rotterdam, The Netherlands. However, also outside of the (academic) hospitals, applications of using genetic information are explored, such as in population screening programs, e.g., for breast cancer or Familial Hypercholesterolemia. This has led to the creation of a new plan for implementing genomics in healthcare and prevention across Europe, called the European Genome Program (EGP). The EGP is planned together with several directorates of the EC and several EU-funded initiatives (such as BBMRI-ERIC) and will encompass sequencing >1,000,000 genomes and genotyping >100 million (richly phenotyped) samples across Europe. I will describe aspects of these developments, highlight examples, and provide an outlook to the future of genomics in Europe.