Abstract
STUDY OBJECTIVES: Individuals with evening chronotype have a higher risk of cardiovascular and metabolic disorders, although the underlying mechanisms are not well understood. In a population-based cohort, we aimed to investigate the association between chronotype and 242 circulating proteins from three panels of established or candidate biomarkers of cardiometabolic processes. METHODS: In 2,471 participants (49.7% men, mean age 61.2 ± 8.4 SD years) from the EpiHealth cohort, circulating proteins were analyzed with a multiplex proximity extension technique. Participants self-reported their chronotype on a five-level scale from extreme morning to extreme evening chronotype. With the intermediate chronotype set as the reference, each protein was added as the dependent variable in a series of linear regression models adjusted for confounders. Next, the chronotype coefficients were jointly tested and the resulting p-values adjusted for multiple testing using a false discovery rate (5%). For the associations identified, we then analyzed the marginal effect of each chronotype category. RESULTS: We identified 17 proteins associated with chronotype. Evening chronotype was positively associated with proteins previously linked to insulin resistance and cardiovascular risk, namely retinoic acid receptor protein 2, fatty acid-binding protein adipocyte, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1). Additionally, PAI-1 was inversely associated with the extreme morning chronotype. CONCLUSIONS: In this population-based study, proteins previously related to cardiometabolic risk were elevated in the evening chronotypes. These results may guide future research in the relation between chronotype and cardiometabolic disorders.