Approved Research

Gene-Environment Interaction Approach to Study Genomic Factors Associated with Common Complex Traits and Diseases

Lay summary

Traditional health research approaches tend to focus on a single risk factor at a time: genetics or environment. Often, however, both act together to determine the outcome. For example, asthma is affected by genetic susceptibility and air pollutants. To represent real-world conditions, both should be taken into account. Here, we will use comprehensive genetic, health, and lifestyle data to understand how Gene-Environment interactions affect health and disease by developing methods that incorporate the UK Biobank data with sunlight data from the TEMIS weather database. In this 3 year project, we will first study the effect of sun exposure in two pilot cases: vitamin D level and skin cancer, then apply our methods to study Gene-Environment interactions in other medical conditions recorded in the UK Biobank. In each case, we will investigate what genetic variants (i.e. differences in individuals' genetic sequences) are associated with the condition and how the effect of these variants changes when we account for environmental factors like sunlight.

Sunlight may improve vitamin D level but increase the risk of skin cancer. Vitamin D is an interesting case because it is essential in healthy immunity and bone development, but also affects other illnesses, like cancer and asthma. Vitamin D is mainly produced in the skin when exposed to sunlight, and can be affected by duration of sun exposure, diet, and lifestyle. As such, populations at higher latitudes or leading indoor lifestyles may be more likely to experience vitamin D deficiency. Similarly, skin cancer risk and survival vary depending on the duration and intensity of sun exposure, age, genetics, and other factors. Overall worldwide rates of skin cancer are increasing. Malignant melanoma, the most serious skin cancer type, has an incidence rate of approximately 4% in Europe. In the UK, melanoma is the fifth most common cancer and rising. In Ireland, skin cancer is the most common cancer, with melanoma being rare but increasing.

So, we will investigate how sun exposure interacts with genetics to determine an individual's vitamin D level or risk of skin cancer or other diseases. This research can inform public health guidance on vitamin D deficiency and cancer prevention. For example, cancer screening programmes can increase screenings for individuals with higher genetic risk factors. In general, understanding the interaction of genetics and environment will help us improve public health measures by advancing our insight into the underlying factors, especially modifiable environmental factors like sun exposure.