Genomic Influences on Susceptibility and Severity of Rheumatoid Arthritis

Genetics in rheumatoid arthritis (RA) has moved from the finding of HLA-shared epitope decades ago toward the understanding of the role of HLA in RA and the findings of ∼100 additional genetic risk variants for disease susceptibility as well as several risk variants for severe disease. These findings increased our understanding of RA abnormality. Still, the mechanisms by which many of the variants exhibit their effect are not yet understood.

Key points

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Genetic studies have increased our understanding of rheumatoid arthritis (RA), pointing out the importance of HLA-DRB1 HLA-B and HLA-DPB1, JAK-STAT signaling, NF-kB, and T-cell receptor signaling.
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The genetics of RA severity is challenging because of the variability of the phenotype, the large amount of data needed, and the interactions with environment.
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The heterogeneity within RA hampers the findings of strong genetic associations.
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The combination of genetic risk factors into a Genetic Risk Scores creates a fairly good predictive model, but its clinical applicability is yet limited.
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Future studies are needed that focus on the functional understanding of the found genetic variants as well as on the development of methods that can encompass with the complexity of RA development.