Researchers Uncover Gene Variations Linked to RA, Other Immune Diseases

Researchers Uncover Gene Variations Linked to RA, Other Immune Diseases

A large-scale genetic study, in combination with information from electronic health records (EHRs), identified new human leukocyte antigen (HLA) associations with several immune conditions, including rheumatoid arthritis and multiple sclerosis.

The findings were reported in the study “Phenome-wide scanning identifies multiple diseases and disease severity phenotypes associated with HLA variants,” and published in the journal Science Translational Medicine, and enabled the creation of the first comprehensive catalog of diseases associated with HLA variations.

This report supports not only the power of EHRs to advance the understanding, treatment and, ultimately, prevention of medical conditions, but the fact that they also may help identify individuals who are at risk of developing specific illnesses.

HLAs are proteins that all cells express to enable the immune system to correctly distinguish host tissues from those of an external source, such as invading microorganisms. Small genetic mutations have been linked to adverse drug reactions and rejection of transplanted organs. However, these variations also have been associated with causing the immune system to misidentify cells and tissues from the body as being from an external source, leading to the development of autoimmune diseases, such as Type 1 diabetes and rheumatoid arthritis.

Previous studies have identified associations between HLA variations and specific symptoms or characteristics of a medical condition.

In this study, the authors evaluated the association of HLA variations with multiple medical conditions simultaneously. This provided a more integrative and broader view of the potential associations.

Taking advantage of DNA databases maintained at Vanderbilt University Medical Center (VUMC) and the Marshfield Clinic Personalized Medicine Research Project in Marshfield, Wisconsin, researchers estimated which HLAs variants would be expressed in nearly 37,300 individuals and linked them to about 1,400 medical conditions collected from EHRs.

This new approach confirmed previously described HLA associations with Type 1 diabetes. It also uncovered evidence for several new potential associations with autoimmune diseases such as rheumatoid arthritis.

“Just imagine what we’ll be able to do with a million people,” Jason Karnes, the study’s co-first author, said in a press release. “That will produce truly comprehensive catalogs of all these kinds of associations across HLA and everything else. The detail with which we’ll be able to resolve these questions will be staggering,” he said.

The results of this study can be accessed freely as a web catalog at, and can be used for further HLA-related research studies.

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