Specifically, samples from the two cohorts were divided into four groups: i) first degree relatives of RA patients without any ACPA or RF positivity and disease symptoms as controls (FDR 1), ii) first-degree relatives with RA associated auto-immunity defined by serum ACPA and/or RF positivity (FDR 2), iii) first-degree relatives having RA specific symptoms with/without ACPA and/or RF autoantibodies (FDR 3), and iii) chronic RA patients (cRA) (see Table 1 for details). This evidence concerns the gene PRTN3 and rheumatoid arthritis.