Assessing the impact of circadian clock genes on inflammatory bowel disease

Summary

Every human has a body clock, which uses the sun's light to set the body's daily (circadian) rhythm. There is an established role for circadian rhythms in controlling the immune system. Environmental disruptors of our circadian rhythm, for example shift work, can increase the risk of diseases driven by chronic inflammation such as inflammatory bowel disease (IBD).

Each human’s circadian rhythm controls whether we are early larks or night owls, termed our chronotype. This behaviour is controlled in part by variation in clock genes. Evening-chronotypes are more likely to have higher fatigue scores in IBD, which is linked to a lower quality of life for patients. Genetic variation (polymorphism) in a clock gene has also been related to a more severe form of Crohn’s disease. This stimulates our interest to further understand links between circadian rhythms and the causes of IBD.

The NIHR IBD BioResource provides a unique opportunity to explore these links in a large group of patients with IBD. This project therefore aims to study the difference in IBD disease patterns that may result from changes in human circadian, or diurnal rhythmic behaviour.

The second aim is to study the impact of circadian misalignment and sleep traits on IBD, using patients with extreme chronotypes and sleep disturbances. We can use genetic instruments to test causality (Mendelian randomisation). These data have potential to improve treatment options for patients with IBD.