Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility genetic risk loci (regions). A research study published in the journal Nature Communications earlier this year identified ten new genome-wide significant regions in Sjögren’s cases of European ancestry, nearly doubling the total number of identified genetic risk loci from 12 to 22. Unfortunately, this list lags behind the over 120 risk loci identified for lupus or rheumatoid arthritis.
A type of study such as a genome-wide association study (GWAS) is done by scanning the genome – the entire set of DNA instructions found in cells – of many people to look for variants that occur more frequently in those with a specific disease than in those without it. An international team of researchers drew on data from a total of 3,885 patients with Sjögren’s and 23,725 people with European ancestry who did not have the disease to serve as controls. These individuals came from many countries including Australia, Austria, France, Germany, Hungary, Italy, Norway, Spain, Sweden, Switzerland, the U.K., and the U.S.
People with multiple mutations in these loci had more than 12 times increased risk to develop Sjögren’s. The variants most likely to raise the risk were predicted to play a role in how genes are turned on and off in immune cells and cells of the salivary glands, both of which go awry.
A further analysis of variants lying in a region known as the human leukocyte antigen (HLA) accounted for most of the genetic burden. HLA are proteins found on most cells in the body. The immune system uses these markers to recognize which cells belong in the body and which do not. They also identified variants that link salivary glands to infection by the Epstein-Barr virus (EBV) that may contribute to Sjögren’s by increasing the number of immune cells that attack the body’s own healthy cells.
The researchers also noted that further mapping of these loci could help develop ways to improve disease pathology, early diagnosis, and treatment of Sjögren’s.
Khatri, B., Tessner, K., et.al. Nature Communications, 2022.