Melatonin, lifestyle, and health: a gene-environmental investigation in the UK Biobank

The hormone melatonin produced by the pineal gland during darkness is well-known for its pleiotropic functions in the human body. Experimental research has demonstrated that melatonin is a strong antioxidant, possesses anti-cancerogenic properties, and reduces the activity of peripheral glands, including the pancreatic islets. Various lifestyle factors are known to alter melatonin production, including daytime light exposure, evening artificial light, caffeine, and physical activity. In addition to these lifestyle factors, it has been shown that a common polymorphism in the melatonin receptor 1 B gene (MTNR1B) also alters nocturnal melatonin secretion. Several studies have established a link between this genetic polymorphism and the risk of type 2 diabetes. However, whether lifestyle known to alter melatonin production may moderate associations between common polymorphisms in MTNR1B and risk of type 2 diabetes has not been investigated in large-scale cohorts, such as the UK biobank. Surprisingly, although melatonin possesses cardio-protective and anti-cancerogenic properties, to our best knowledge no study to date has examined whether common polymorphisms in MTNR1B increasing the release of nocturnal melatonin may reduce the disease risk for cardiovascular events (such as myocardial infarcts) and cancers (such as prostate cancer, breast cancer, and colocorectal cancer) frequently found in the general population. With all these gaps in mind, our project has three specific aims:
1. To verify whether subjective parameters of sleep, including sleep duration, chronotype, and sleep disturbances moderate associations between common polymorphisms in the melatonin receptor 1 B gene (MTNR1B) and risk of type 2 diabetes in a large population.
2. To investigate whether diet (e.g. caffeine consumption), light exposure (e.g. time of outdoor activities), and other lifestyle factors moderate associations between common polymorphisms in MTNR1B and risk of type 2 diabetes.
3. To investigate whether common polymorphisms in MTNR1B modify the disease risk for cardiovascular events (such as myocardial infarcts) and highly prevalent cancers (such as prostate cancer, breast cancer, and colocorectal cancer).
Findings of this project are likely to provide valuable insight into possible gene-environmental interactions in the pathogenesis of type-2 diabetes, cardiovascular diseases, and cancer.