Importantly, we have also shown in a prospective longitudinal cohort of at-risk, but unaffected first-degree relatives (FDR) of Indigenous North Americans (INA) that only a proportion of individuals in whom ACPA are detected at any specific timepoint will actually go on to develop RA, and indeed many seropositive individuals become seronegative over time (5). The gene discussed is PRTN3; the disease is rheumatoid arthritis.