Various immune-related diseases have a strong genetic overlap

This has emerged from an analysis by geneticists at the University Medical Center Groningen of all globally conducted association studies of these diseases. The analysis reveals that although the diseases have different manifestations, they also have a major, comparable origin.

This is a significant advance in our understanding of why patients can have several diseases at the same time, and why they occur more frequently within families. They have published their findings in the latest edition of Nature Reviews Genetics, which appeared online on 18 December 2008 and in which they investigate the joint genetic origins of various immune-related disorders.

Between 5 and 10 % of the population have auto-immune and chronic inflammatory diseases such as type 1 diabetes, coeliac disease, Crohn’s disease and rheumatoid arthritis. Patients with these diseases often have problems with chronic infections and their immune systems often react against their own tissue. This often leads to chronic infection reactions in, for example, the joints in the case of rheumatism and the large intestine in the case of Crohn’s disease. Cases are known where patients have more than one of these immune-related diseases, or that several family members are affected. Earlier studies have shown that heredity plays a role in the emergence of these diseases.

Human DNA has hundreds of thousands of tiny variations, which in most cases are insignificant. For a number of years now it has been possible to use these DNA variations to trace genes involved in the occurrence of all kinds of diseases. This is done by searching for variants in the DNA that are more common in ill people than in healthy ones. To this end, about 300,000 variants were analysed for each individual, a genome-wide association study. This technique has in recent years been used often for immune-related diseases and as a result many genes that play a role in these diseases have been identified.

Family studies had already revealed that there was possibly a joint hereditary basis underlying various immune-related diseases. Researchers from the department of Genetics of the UMCG have conducted an extensive analysis of all the genome-wide association studies of these diseases that have been carried out anywhere in the world.

This resulted in a study of 11 immune-related diseases. It appears that 23 genes are involved in at least two immune-related diseases; each of these 23 genes is associated with at least two diseases. In addition, further research revealed that the function of these genes overlaps. Many of these genes play a role in the development of the type of reaction by the immune system (Th1, Th2 or Th17) and which immune cells are activated as a result (T cells, B cells). This clearly revealed the way that the immune reaction is disturbed and that also provides possible reference frameworks for treatment (medication or perhaps vaccination).

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