Polygenic risk scores for rheumatoid arthritis and idiopathic pulmonary fibrosis and associations with RA, interstitial lung abnormalities, and quantitative interstitial abnormalities among smokers.
Authors
Affiliations (13)
Affiliations (13)
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
- Harvard Medical School, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Pulmonary, Allergy, Sleep and Critical Care Medicine Section, Department of Medicine, VA Boston Healthcare System, West Roxbury, MA, USA.
- Harvard Medical School, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA; Université de Paris Cité, INSERM UMR 1152, F-75018 Paris, France; Service de Rhumatologie, Hôpital Bichat-Claude Bernard, AP-HP, F-75018 Paris, France.
- Harvard Medical School, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
- Colorado School of Public Health, Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
- Division of Rheumatology, Mayo Clinic, Rochester, MN, USA.
- Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, VA, USA.
- Division of Rheumatology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
- Division of Rheumatology, National Jewish Health, Denver, CO, USA.
- Division of Pulmonary and Critical Care Medicine, South Shore Health, South Weymouth, MA, USA.
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
Abstract
Genome-wide association studies (GWAS) facilitate construction of polygenic risk scores (PRSs) for rheumatoid arthritis (RA) and idiopathic pulmonary fibrosis (IPF). We investigated associations of RA and IPF PRSs with RA and high-resolution chest computed tomography (HRCT) parenchymal lung abnormalities. Participants in COPDGene, a prospective multicenter cohort of current/former smokers, had chest HRCT at study enrollment. Using genome-wide genotyping, RA and IPF PRSs were constructed using GWAS summary statistics. HRCT imaging underwent visual inspection for interstitial lung abnormalities (ILA) and quantitative CT (QCT) analysis using a machine-learning algorithm that quantified percentage of normal lung, interstitial abnormalities, and emphysema. RA was identified through self-report and DMARD use. We investigated associations of RA and IPF PRSs with RA, ILA, and QCT features using multivariable logistic and linear regression. We analyzed 9,230 COPDGene participants (mean age 59.6 years, 46.4 % female, 67.2 % non-Hispanic White, 32.8 % Black/African American). In non-Hispanic White participants, RA PRS was associated with RA diagnosis (OR 1.32 per unit, 95 %CI 1.18-1.49) but not ILA or QCT features. Among non-Hispanic White participants, IPF PRS was associated with ILA (OR 1.88 per unit, 95 %CI 1.52-2.32) and quantitative interstitial abnormalities (adjusted β=+0.50 % per unit, p = 7.3 × 10<sup>-8</sup>) but not RA. There were no statistically significant associations among Black/African American participants. RA and IPF PRSs were associated with their intended phenotypes among non-Hispanic White participants but performed poorly among Black/African American participants. PRS may have future application to risk stratify for RA diagnosis among patients with ILD or for ILD among patients with RA.