Ss58-02 Shift Work Tolerance and Chronic Disease Risk: The Role of Individual Susceptibility

This is the authors' abstract. We don't add key points for this paper.

Introduction Significant health effects of chronic clock dysregulation have long been described, prompting e.g., the World Health Organization to classify night work as a probable carcinogen. As a next ground-breaking step, we aim to identify the night-active individual who develops disease. Materials and Methods Using cutting-edge techniques in varied populations, we explore the concept of clock resilience by constructing a genetic shift work tolerance/clock resilience score based on traits considered relevant for clock resilience, to identify those at greatest risk of developing disease. Results We will present the stages of developing a multi-polygenic risk score (MPRS) for the complex trait of clock resilience, i.e. ‘shift work tolerance’, using previously published large-scale genome-wide association studies (GWAS) and weighted allele scores for selected traits (e.g., chronotype, seasonality, melatonin), adding also specific clock-related SNPs of particular importance, e.g., a variant in the melatonin receptor MTNR1B, which has been linked to type 2 diabetes, SNPs from an agnostic GWAS of our defined shift work disorder, as well as polygenic risk scores for the respective outcomes under investigation (non-communicable diseases such as type 2 diabetes, cardiovascular disease, depression, cancer) to adjust for genetic disease risk. Conclusions The large number of night workers and night-active individuals, which is likely to rise in Europe and globally, calls attention to the high relevance of shift-work related disease. Our work aims to deliver the profile of an individual, including their genotypic variation, involved in the risk of developing chronic disease if they are exposed to circadian misalignment in the form of night shift work.