Approved research

A multi-polygenic score of clock resilience and its utility in predicting vulnerability to night work with regards to chronic disease risk (cardiovascular disease, type 2 diabetes, depression, breast)

Lay summary

Virtually every cell of our body follows the 24-hr circadian rhythm of a hypothalamic master pacemaker that evolved in the natural light-dark cycle. Decoding this biologic clock culminated in the Nobel Prize in Physiology or Medicine 2017 for the discovery of molecular mechanisms controlling the circadian rhythm. It is now recognized that a strong, unperturbed biologic clock is a hallmark of healthy aging. The introduction of electric light, however, presents unique challenges: today, 20% of the global work force engages in alternate working hours associated with light in unnatural times (eg. night work). Increases in the risk of major chronic disease and mortality have been associated with night work. Further, the ubiquity of light at night implicates potential risk for everyone. This 5-year project targets the urgency of preventing adverse health consequences of a challenged clock. It does so by aiming to decipher individual risk and related mechanisms 1) using a cutting-edge multi-polygenic score approach; 2) employing transgenerational and deeply phenotyped cohort approaches; and 3) carrying out interventions using genetic risk stratification. The ultimate aims of this project are to 1) identify the night worker who develops disease, 2) profile mechanisms involved, and 3) optimize effectiveness of interventions to improve sleep and shift work disorder, facilitating immediate implementation of far reaching risk-based prevention strategies/policies, aimed at promoting healthy aging despite clock challenges.