Relative contributions of family history and a polygenic risk score on COPD and related outcomes: COPDGene and ECLIPSE studies

BMJ Open Respir Res. 2020 Nov;7(1):e000755. doi: 10.1136/bmjresp-2020-000755.


Introduction: Family history is a risk factor for chronic obstructive pulmonary disease (COPD). We previously developed a COPD risk score from genome-wide genetic markers (Polygenic Risk Score, PRS). Whether the PRS and family history provide complementary or redundant information for predicting COPD and related outcomes is unknown.

Methods: We assessed the predictive capacity of family history and PRS on COPD and COPD-related outcomes in non-Hispanic white (NHW) and African American (AA) subjects from COPDGene and ECLIPSE studies. We also performed interaction and mediation analyses.

Results: In COPDGene, family history and PRS were significantly associated with COPD in a single model (PFamHx <0.0001; PPRS<0.0001). Similar trends were seen in ECLIPSE. The area under the receiver operator characteristic curve for a model containing family history and PRS was significantly higher than a model with PRS (p=0.00035) in NHWs and a model with family history (p<0.0001) alone in NHWs and AAs. Both family history and PRS were significantly associated with measures of quantitative emphysema and airway thickness. There was a weakly positive interaction between family history and the PRS under the additive, but not multiplicative scale in NHWs (relative excess risk due to interaction=0.48, p=0.04). Mediation analyses found that a significant proportion of the effect of family history on COPD was mediated through PRS in NHWs (16.5%, 95% CI 9.4% to 24.3%), but not AAs.

Conclusion: Family history and the PRS provide complementary information for predicting COPD and related outcomes. Future studies can address the impact of obtaining both measures in clinical practice.

Trial registration: NCT00292552 NCT00608764.

Keywords: COPD epidemiology; emphysema; tobacco and the lung.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans
  • Humans
  • Pulmonary Disease, Chronic Obstructive* / epidemiology
  • Pulmonary Disease, Chronic Obstructive* / genetics
  • Pulmonary Emphysema*
  • Risk Factors
  • Treatment Outcome
  • Whites / genetics

Associated data