Smoking is the best-established risk factor for RA and may contribute to disease progression through gene-environment interactions by inducing localized mucosal inflammation in the airways and other anatomic sites, protein citrullination (a post-translational modification from arginine to citrulline), and downstream formation of anti-citrullinated protein antibodies leading to RA autoimmunity [17,18,19,20,21,22,23,24,25]. The gene discussed is PROS1; the disease is Autoimmunity.