Physical workload is associated with increased risk of rheumatoid arthritis: results from a Swedish population-based case–control study

OBJECTIVES This study investigated: (1) the association of physical workload (PW) and risk of rheumatoid arthritis (RA); (2) the potential interactions between PW and the genes in the human leucocyte antigen (HLA) region. METHODS A population-based case-control study involving incident cases of RA (3150 cases and 5130 controls) was performed using data from the Swedish Epidemiological Investigation of Rheumatoid Arthritis. Information on 7 types of self-reported PW exposure and HLA-DRB1 genotypes of cases and controls were gathered. Anticitrullinated protein antibody (ACPA) status of cases was identified. For each PW exposures, exposed participants were compared with unexposed participants. ORs with 95% CIs of RA (overall), ACPA-positive RA and ACPA-negative RA associated with different PWs were estimated using logistic regression. HLA-PW interactions were estimated using the principle of departure from additivity of effects by calculating attributable proportion (AP) due to interaction. RESULTS ORs of developing RA associated with 6 various PW exposures ranging from 1.3 (95% CI 1.1 to 1.4) to 1.8 (95% CI 1.6 to 2.0) were observed. Exposure to more types of PW was associated with increasing risk for RA (p<0.0001). No major difference in the ORs between ACPA-positive and ACPA-negative RA was found. For some exposures, we found evidence of interactions between PW and the HLA-DRB1 shared epitope genes, regarding risk of ACPA-positive RA (AP: from 0.3 (95% CI 0.1 to 0.5) to 0.4 (95% CI 0.2 to 0.6)). CONCLUSIONS PW is associated with the risk of ACPA-positive and ACPA-negative RA. Interactions between PW and the HLA-DRB1 shared epitope were found in ACPA-positive RA.