Incidental or secondary findings in genetics : stairways to a life of certainty?

Since science started to unravel the human genome, the idea has risen that we are discovering the building blocks and the blueprint of life. Physical qualities, health and illness and even character traits turned out not to be determined by accident or fate, but to be the result of a constant interaction between behavior, environmental factors and very specifically organized DNA strands. As genetic knowledge still increases at high speed and more genes and their function get revealed, the human possibilities for action and prevention, also on the level of healthcare, keep on growing. In some cases, illness can even be prevented, which might create the impression of a predictable health trajectory. If, despite this promising evolution, illness strikes, patients’ questions are tried to be answered as good as possible, i.a. by use of genetic testing. Over the last few years, the technology of Next Generation Sequencing (NGS), by means of which the whole exome or genome is analyzed, has been introduced in the diagnostic context and it is most likely that NGS’s application as a diagnostic tool will only increase in the future. However, NGS might not only answer the initial questions but it might also reveal additional information and (initially) unsought-for health risks, as incidental or secondary findings (ISFs). According to the (currently utopian) dream of a perfectly predictable future, genomic information seems to be a valuable tool. This genetic knowledge might raise the idea that it will be possible to predict which illness one will get, at what time the first symptoms will appear and which prevention or treatment will be most effective. ISFs can stimulate this feeling of knowledge and control, as they might offer an extra chance to avoid serious morbidity or to prepare for future health evolutions. However, one might wonder if this feeling of certainty and control is legitimate and whether the utopian dream can ever be realized. Currently, scientific knowledge is lacking on many genes’ function and on the actual pathogenicity of many variants. Moreover, due to incomplete penetrance and variable expression, pathogenic variants do not indicate a delineated truth but a wide spectrum of possible futures, while also many environmental factors can influence the final outcome. Therefore, ISFs might not only be a way towards certainty and security but also towards doubts, uncertain knowledge, hesitation and worries. To realize a better understanding of the status of ISFs, we have set up a qualitative study and we have been interviewing patients with a Mendelian disease about their experience with NGS and the meaning they ascribe to ISFs. In our presentation, we will focus on patients’ ideas regarding the possible knowledge of additional genetic predispositions. How is this information perceived as contributing to a feeling of certainty? Are ISFs hidden stairways to control? Or will patients get off-road, confused by the many possible ways to go