DNA based screening in prevention: current practise and future promise

Abstract Some rare diseases are caused by variants in single genes. In total rare diseases affect 36 million people in Europe. DNA testing increasingly makes it possible to identify individuals with rare genetic conditions before irreparable damage has occurred. Neonatal screening programs include up to 40 conditions in Europe, and most of these are genetic conditions. Testing often is first of all done with biochemical methods, assessing metabolites or enzyme activity. DNA testing is increasingly used in neonatal screening programs, often as second tier. Pilot studies investigate screening of hundreds of genes in thousands of infants with DNA-sequencing technology. Challenges nowadays concern the selection of disease to be included and the variant interpretation. Furthermore, after referral the follow-up must be well organized. For adults, family members of cancer patients or cardiovascular disease patients can be invited for systematic cascade screening when they are at 50% or 25% risk, but few public health programmes have integrated such an approach. Population cancer screening programmes also might profit from testing of multiple genes, both high risk genes as well as polygenic risk scores, but the integration of DNA information in public health screening programmes is not foreseen in the near future. Research projects integrating DNA information in stratified screening programmes are ongoing. Challenges of DNA information for public health applications include the cost, the variant interpretation and the predictive value. An important strategic question is how to collect the data that would be needed for future decision making. Are the available resources on healthy populations sufficient to inform decision making on public health screening programs? Furthermore, how can stakeholders in public health and genetics collaborate to achieve responsible innovation?