Moreover, it was previously established that associations between HLA-DRB1 SE and tobacco smoking appeared at the CSA stage, while associations with autoantibody positivity (ACPA, RF) and severe disease appeared later at the RA onset, which is suggested when FDR from RA patients and early-RA patients are studied (31–33). The gene discussed is HLA-DRB1; the disease is rheumatoid arthritis.