Association between dim light melatonin onset predicted from gene expression profiles with sleep time and chronotype preference: A pilot study

Chronotherapeutic approaches that optimize the timing of therapy to enhance efficacy and minimize side effects are becoming mainstream. The widespread adoption of chronotherapeutic approaches is hindered by the lack of accessible, valid tools to determine circadian time. Building on evidence that gene expression profiles predict circadian time, this pilot study assessed associations between circadian phase predictions from a single blood sample, actigraphy-estimated sleep, and chronotype in a real-world setting. Twelve adults (mean age 51 y, 8 women) reporting short sleep (<7 h/night) and at risk for metabolic syndrome participated. CD14+ monocytes were isolated from 20 ml blood samples, pelleted, and stored at -80°C before RNA sequencing. Sleep was monitored over two weeks using the ActiGraph GT9X-BT, and chronotype preference was assessed with the Composite Scale of Morningness. Spearman's correlations analyzed correlations between predicted dim light melatonin onset (DLMO), sleep, and chronotype preference. Moderate-to-strong association was found between gene expression-based DLMO predictions and sleep, supporting the utility of peripheral blood mononuclear cell gene expression profiles for estimating circadian phase. This approach shows promise for improving chronotherapy implementation in middle-aged adults with chronic health conditions and short sleep. This study was part of a larger study that was registered with Clinicaltrials.gov as NCT03596983.