Development and External Validation of a Genetic Risk Score for Pain in Rheumatoid Arthritis

Area of Science:

• Genetics
• Rheumatology
• Pain Medicine

Background:

• Single-nucleotide polymorphisms (SNPs) are implicated in chronic pain syndromes.
• Understanding genetic contributions to pain in rheumatoid arthritis (RA) is crucial for personalized treatment.

Purpose of the Study:

• To investigate the association between genetic variants and pain/disease activity in rheumatoid arthritis (RA).
• To develop and validate a genetic risk score (GRS) for pain in RA patients.

Main Methods:

• Utilized two independent RA cohorts (FORWARD and VARA) for training and validation.
• Calculated a pain-related genetic risk score (GRS) based on 36 fibromyalgia-associated SNPs.
• Employed multivariable linear regression and generalized estimating equations to analyze GRS associations with pain and disease activity.

Main Results:

• The study included 756 participants from FORWARD and 2,176 from VARA.
• Higher quartiles of the pain GRS were significantly associated with increased baseline pain in the VARA cohort.
• Elevated GRS predicted greater pain and higher disease activity throughout follow-up in VARA participants.

Conclusions:

• Genetic risk scores derived from pain-associated SNPs demonstrate a significant link to RA pain and disease activity.
• These findings highlight the clinical relevance of genetic pain predisposition in managing RA.
• Genetic factors influencing pain may affect treatment response and the likelihood of achieving remission in RA.