Sibling study maps genetic clusters in 22 autoimmune diseases

In Swedish national registers, the records of nearly 3.84 million sibling pairs became a map of shared risk. Researchers used data from more than 6.3 million individuals born between 1932 and 1983 to study 22 autoimmune diseases from 1969 to 2013, finding an extensive network of genetic connections and distinct clusters, but no strong common genetic basis for all of them.

The method was broad but focused. By comparing how diseases occurred among siblings, the researchers estimated the extent to which different conditions share genetic risk. The work brought together researchers from Karolinska Institutet, Uppsala University, the University of Gothenburg, Örebro University, Region Värmland and international partner institutions. Jakob Skov, an associate professor at Karolinska Institutet's Department of Medicine, Solna, said earlier research had mostly examined individual disease pairs or smaller groups.

The resulting map separated several families of disease. Connective tissue diseases, endocrine autoimmune diseases and autoimmune gastrointestinal diseases each formed distinct genetic clusters. Diseases affecting the nervous system had weaker genetic links to one another. Among the strongest associations were psoriasis with psoriatic arthritis, autoimmune hepatitis with primary biliary cholangitis, and systemic lupus erythematosus with Sjögren's syndrome. Multiple sclerosis stood out for its relatively weak genetic associations with most of the other diseases studied.

For patients and family members, the near-term value is a clearer awareness of related autoimmune risks. The researchers say the findings may help people and their relatives recognize connections between conditions that have often been studied separately. The study found no evidence that all autoimmune diseases share a strong common genetic basis, while some show recognizable genetic groupings.

The scale also made it possible to study common and rare conditions together. More than 707,000 people, or 11.2% of the study population, had at least one autoimmune disease, while around 1.3% had more than one diagnosis. The study, published in the Journal of Clinical Investigation, carries an important limitation: a sibling model cannot fully distinguish genetic factors from certain environmental factors shared within families.