Rheumatoid arthritis

Rheumatoid arthritis is an autoimmune disease that attacks the joints. This score sums common variants affecting susceptibility.

What this rheumatoid arthritis score reads

This is PGS004118, from the same 2024 five-biobank benchmarking study, built from a GWAS of 311,292 people that was unusually East Asian led: about 81% East Asian and 19% European ancestry. It uses 91 variants.

Its largest weight sits at the 1p13 locus containing PTPN22, an immune signalling gene whose best-known variant, R620W, this site reads on its own page. The score's variant there tags the same signal.

How well it predicts rheumatoid arthritis

Across the five biobanks, each standard deviation higher score carried odds ratios from 1.30 to 1.71 for seropositive rheumatoid arthritis, with areas under the curve of 0.57 to 0.65 and variance explained of 1.1% to 3.3%.

Note that all of that is for seropositive disease, meaning cases with anti-CCP or rheumatoid factor antibodies. Seronegative rheumatoid arthritis has a different genetic profile and is not what this score was measured against.

What this score misses, starting with HLA

The largest genetic risk factor for rheumatoid arthritis is not in this score. Specific HLA-DRB1 alleles, collectively called the shared epitope, carry effects far larger than any variant here, and they sit in a region so variable that consumer genotyping chips cannot type it reliably.

Smoking is the strongest known environmental factor, and it interacts with those HLA alleles rather than adding to them independently, which is one of the clearest gene-environment interactions in autoimmunity. A score built from common variants outside HLA cannot represent any of that.

How to read a high or low score

Rheumatoid arthritis affects roughly 0.5 to 1% of adults, so relative risks of this size still leave absolute risk low. Nothing about a percentile calls for testing without symptoms.

Persistent joint swelling and pain, particularly in the small joints of the hands and feet, with morning stiffness lasting more than half an hour, is what should prompt medical assessment. Early treatment materially changes outcomes in rheumatoid arthritis, which is a better reason for attention than a score.

Ancestry and accuracy

This is one of the few scores here whose source GWAS was majority non-European. It was developed and mainly evaluated in European-ancestry biobanks, however, so the usual caution applies in both directions: strong evidence for none of the populations at the extremes of its own composition.

How much of this score your file covers

All 91 variants in the published score are present in a standard consumer DNA file, so this reconstructs the published score in full.

Common questions

Is rheumatoid arthritis inherited? Partly. Twin and family studies show a substantial genetic component, but most of it sits in the HLA region, which this score does not read, and smoking is a major environmental contributor. A polygenic percentile captures only a slice of the picture.

Does a high score mean I should get tested for rheumatoid factor? No. Antibody tests are used to evaluate symptoms, not to screen people who feel well, and testing without symptoms mostly produces false positives to worry about.

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