Autoimmune diseases form distinct genetic clusters, study finds

Different autoimmune diseases often share genetic risk factors, but not through a single common genetic vulnerability. In a new study published in The Journal of Clinical Investigation, researchers from Karolinska Institutet and collaborating institutions show that autoimmune diseases instead form genetic clusters that largely reflect the tissues or organs they affect.

Autoimmune diseases arise when the immune system mistakenly attacks the body's own tissues. Researchers have long known that these diseases tend to run in families, but the genetic relationships between different autoimmune diseases have remained unclear.

In the current study, the researchers analyzed data from Swedish national registers. The material included more than 6.3 million individuals born between 1932 and 1983, including nearly 3.84 million sibling pairs. In total, 22 autoimmune diseases were studied over the period 1969 to 2013.

The researchers found that more than 707,000 individuals, corresponding to 11.2 per cent of the study population, had at least one autoimmune disease. Around 1.3 per cent had more than one such diagnosis.

No common genetic basis

By studying how diseases occurred among siblings, the researchers were able to estimate the extent to which different diseases share genetic risk. The results revealed an extensive network of genetic connections between autoimmune diseases. At the same time, the study found no evidence that all autoimmune diseases share a strong common genetic basis.

Instead, distinct groups of related diseases emerged. Connective tissue diseases, endocrine autoimmune diseases and autoimmune gastrointestinal diseases each formed separate genetic clusters. Diseases affecting the nervous system, by contrast, showed weaker genetic links to one another.

Previous knowledge of how autoimmune diseases are related has mainly been based on studies of individual disease pairs or smaller groups of the most common conditions. This study provides a much broader picture and shows, from a wider perspective, how different diseases share genetic risk."

Jakob Skov, associate professor, Department of Medicine, Solna, Karolinska Institutet

Multiple sclerosis stood out

Some of the strongest genetic associations were observed between psoriasis and psoriatic arthritis, autoimmune hepatitis and primary biliary cholangitis, and systemic lupus erythematosus and Sjögren's syndrome. Multiple sclerosis stood out by having relatively weak genetic associations with most of the other autoimmune diseases included in the study.

"This knowledge may help increase awareness of the risk of related autoimmune diseases among patients and their family members," continues Jakob Skov.

The researchers note that the study is based on a very large population dataset, making it possible to investigate both common and rare diseases. One limitation is that the sibling model used cannot fully distinguish genetic factors from certain shared environmental factors.

The study was conducted by researchers from, among others, Karolinska Institutet, Uppsala University, University of Gothenburg, örebro University, Region Värmland, and several international collaborators. The research was funded by the Swedish Society of Medicine, research funding from Region Värmland, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and ALF funding between Region Stockholm and Karolinska Institutet.