Identification of Molecular Targets and prospective follow-up in pre-existing prospective cohorts

A, Cross-sectional characterisation of the relationship between biomarkers of circadian rhythms, sleep disorders, and metabolic state in the population-representative Gutenberg Health Study and the prospective Pietroiusti Study by using state-of-the-art genomics, epigenetics, metabolomics, proteomics, and clinical-physiological technology for each methodological approach based on specific expertise represented in this consortium. A hypothesis-free screening approach of wide-spectrum ‘omics’ technology will be combined with targeted analysis of genes and biomarkers known to be involved in circadian control of metabolism.

B, The prospective Gutenberg Health Study (GHS) and Pietroiusti cohorts are pre-existing cohort studies that have been designed and recruited before the start of the EuRhythDia consortium work. Follow-up investigations will take place according to pre-specified work plans within the two cohorts, and data relevant to the present proposal will be extracted at the end of the funding period from the databases to allow verification of the prospective influence of lifestyle associated with the molecular targets identified in Stages 1 and 2 on incidence of type 2 diabetes mellitus and obesity (primary endpoint). Mortality and incident cardiometabolic disease will be additional, secondary endpoints. Replication of the consortium’s data in the prospective Whitehall II, SardiNIA, and Dallas Heart Study cohorts will be performed based on their existing data sets. Each of these cohorts possesses specific types of data valuable for the consortium: Whitehall II has extensive data on sleep quality from a cohort of 2,751 civil servants of the city of London plus long-term follow-up; SardiNIA has genotyping data from 6,162 participants plus long-term follow-up, and Dallas Heart Study has actigraphic activity measurements from 6,101 participants plus long-term follow-up.

In the Gutenberg Health Study (GHS), diet and physical activity were assessed using validated questionnaires. The SQUASH Questionnaire was used for assessing leisure time physical activity (Wendel-Vos GC, Schuit AJ, Saris WH, Kromhout D. Reproducibility and relative validity of the short questionnaire to assess health-enhancing physical activity. J Clin Epidemiol 2003; 56: 1163-9.). Diet was assessed using a questionnaire developed and validated by the German Institute of Human Nutritition. With these validated questionnaires, robust data are available on the aspects of physical activity and dietary habits to control for the effects of night shift work on measures of glucose metabolism in the statistical analyses based on the GHS cohort.