Identifying shared genetic architecture between rheumatoid arthritis and other conditions: a phenome-wide association study with genetic risk scores.

Background: Rheumatoid arthritis (RA) shares genetic variants with other autoimmune conditions, but existing studies test the association between RA variants with a pre-defined set of phenotypes. The objective of this study was to perform a large-scale, systemic screen to determine phenotypes that share genetic architecture with RA to inform our understanding of shared pathways.

Methods: In the UK Biobank (UKB), we constructed RA genetic risk scores (GRS) incorporating human leukocyte antigen (HLA) and non-HLA risk alleles.

Association of Cigarette Smoking With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Importance: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic small vessel vasculitis characterized by circulating ANCAs targeting proteinase 3 (PR3) or myeloperoxidase (MPO) and associated with excess morbidity and mortality. Myeloperoxidase-ANCA-positive AAV and PR3-ANCA-positive AAV are increasingly recognized to have differences in genetic risk, pathogenesis, and response to treatment. Risk factors for AAV, including cigarette smoking, are poorly understood.