Molecular map reveals genetic origins of 21 autoimmune diseases

Scientists have created a molecular map that pinpoints genetic variants that play a role in 21 different autoimmune diseases, they report Oct. 27 in the journal Nature. 

Researchers at Yale, the University of California-San Francisco (UCSF), and the Broad Institute of MIT and Harvard developed a sophisticated mathematical model and created maps of different cell types that together enabled them to identify which variants cause the immune response to go awry and cause specific diseases. “These findings give new insight into the cause of multiple sclerosis and other autoimmune diseases,” said Yale’s David A. Hafler, the Gilbert H. Glaser Professor of Neurology, professor of immunobiology, chair of the Department of Neurology, and co-senior author of the paper.

Finding the underlying cause of human autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, Crohn’s disease, and diabetes has proved elusive. Intensive investigation of the gene regions in patients with autoimmune disease had identified hundreds of common gene variants shared among these different diseases. But how these variants trigger such a wide variety of diverse diseases was not known.

Researchers used the mathematical model they developed to analyze data from genome-wide association studies of autoimmune patients and found these tiny variations in DNA — called single nucleotide polymorphisms, or SNPs — occurred near master genetic regulators of immune system responses. They then created “maps” from data compiled by the Epigenomics project of National Institutes of Health (NIH), a federally-funded effort to map the regulatory mechanisms of the human genome across a wide range of cell types.