Approved Research

Analyses of IL12B in complex genetic diseases

Lay summary

We have shown that a particular gene, IL12B, has variants associated with increased risk or severity of a number of diseases, including severe childhood asthma, fatal malaria, heart disease and cancer. This gene can be involved in many disease because it has the instructions to make an important protein that is involved in signalling and regulating the immune system, especially early in immune responses. However, the IL12B genetic variants are complicated and people can have one of eight different combinations; from our preliminary studies, each seeming to have different effects. These IL12B variants also are likely to interact differently with other genes to bring about disease. We would like to study and confirm the effects of the different Il12B variants in common diseases. We would also like to identify other genes that IL12B interact with.

Testing hundreds of thousands of genetic markers in patients or from the general population has allowed the identification of disease genes. Such genome-wide association studies have increased our understanding of the basis for many common diseases. However, most of the genes that have been identified contribute only a small amount of the overall risk of disease. Interactions of these genes can increase their impact. There are several methods to test for such interactions. These analyses are challenging because millions of independent interactions have to be calculated over a sample of thousands of patients.

The UK BioBank offers a great opportunity to confirm the role of IL12B in common diseases, and to identify other genes it interacts with. Production of genetic tests that can predict disease risk will allow earlier identification of people at risk of these diseases, allowing earlier intervention and better management. Prevention of CVD, DKD and cancers like melanoma will be very significant for patients and their families, and has the potential for enormous savings for  the national health budget.