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Genetics of rheumatoid arthritis: confronting complexity

Published by National Institutes of Health | U.S. Department of Health & Human Services | Catalog Last Checked: September 07, 2025 at 02:17 PM | Dataset Last Updated: September 06, 2025
The genetic basis for rheumatoid arthritis (RA) is likely to be extremely complex. Even the role of MHC genes remains to be fully defined, and may involve interactive genetic effects. The difficulty of precisely defining the clinical phenotype, as well as underlying genetic heterogeneity, complicates the problem. In addition, stochastic genetic or physiologic events may contribute to the low penetrance of susceptibility genes. This situation parallels developing paradigms for other autoimmune disorders, in which many different genes each appear to contribute a small amount to overall risk for disease, and where severity and specific phenotypic subtypes are subject to genetic effects. The completion of the human genome project, along with advances in informatics, will be required to reach a deeper understanding of RA. It is likely that this will involve an iterative and interactive process between several different scientific disciplines.

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