Approved research

The association between circadian gene polymorphism and human disease

Lay summary

The circadian clock is closely linked to human health, and malfunctions in the clock can result in sleep disorders and other diseases. Our lab is interested in investigating the involvement of circadian clock genes (e.g. Bmal1, Clock, Per2, etc.) in common human diseases such as metabolic disease, cardiovascular diseases, and psychological disorders. The aim of this study is twofold: one is to conduct a quantitative analysis of the enrichment of existing circadian gene mutations in common human diseases, and the other is to identify new circadian gene mutations in human disease patients versus healthy controls, which could provide insights into new circadian regulation mechanisms.

Organisms possess inherent rhythmic systems, known as circadian clocks, that govern their physiological and behavioral functions over a 24-hour cycle. In mammals, the core clock components, which have been well-characterized, include the transcription factors BMAL1/CLOCK and their specific repressor Periods 1-3/Cryptochromes 1-2 (PERs/CRYs). These core clock components form a transcription-translation feedback loop (TTFL) that generates an approximately 24-hour circadian oscillation. Furthermore, the circadian clock plays a crucial role in regulating the physiological functions of nearly all tissues and organs. Disruptions to normal circadian rhythms have the potential to impact a variety of disease-related pathways, as has been extensively studied in model organisms.

Human genetic studies are powerful tools for elucidating the relationship between genes and diseases. Over the past decade, several circadian mutations have been identified in patients with human diseases. These mutations have provided insights into the mechanisms of the circadian clock. However, patient recruitment remains a challenge in this field. Therefore, the UK biobank will serve as a valuable platform for studying circadian gene mutations in patients.

This project will take approximately 36 months to complete. The study will extend our knowledge of the biological function of circadian clock genes and rhythms, and help us understand why circadian rhythms are important and ubiquitous. Identifying mutations in circadian clock genes that potentially alter circadian function could provide insights into the molecular mechanisms of the circadian clock. Furthermore, this study may establish a link between circadian gene mutations and human disease occurrence, providing new ideas for human disease diagnosis and therapy.