TY - JOUR
T1 - Polygenic risk scores identify heterogeneity in asthma and chronic obstructive pulmonary disease
AU - Moll, Matthew
AU - Sordillo, Joanne E.
AU - Ghosh, Auyon J.
AU - Hayden, Lystra P.
AU - McDermott, Gregory
AU - McGeachie, Michael J.
AU - Dahlin, Amber
AU - Tiwari, Anshul
AU - Manmadkar, Monica G.
AU - Abston, Eric D.
AU - Pavuluri, Chandan
AU - Saferali, Aabida
AU - Begum, Sofina
AU - Ziniti, John P.
AU - Gulsvik, Amund
AU - Bakke, Per S.
AU - Aschard, Hugues
AU - Iribarren, Carlos
AU - Hersh, Craig P.
AU - Sparks, Jeffrey A.
AU - Hobbs, Brian D.
AU - Lasky-Su, Jessica A.
AU - Silverman, Edwin K.
AU - Weiss, Scott T.
AU - Wu, Ann Chen
AU - Cho, Michael H.
N1 - Publisher Copyright: © 2023
PY - 2023/12
Y1 - 2023/12
N2 - Background: Asthma and chronic obstructive pulmonary disease (COPD) have distinct and overlapping genetic and clinical features. Objective: We sought to test the hypothesis that polygenic risk scores (PRSs) for asthma (PRSAsthma) and spirometry (FEV1 and FEV1/forced vital capacity; PRSspiro) would demonstrate differential associations with asthma, COPD, and asthma-COPD overlap (ACO). Methods: We developed and tested 2 asthma PRSs and applied the higher performing PRSAsthma and a previously published PRSspiro to research (Genetic Epidemiology of COPD study and Childhood Asthma Management Program, with spirometry) and electronic health record–based (Mass General Brigham Biobank and Genetic Epidemiology Research on Adult Health and Aging [GERA]) studies. We assessed the association of PRSs with COPD and asthma using modified random-effects and binary-effects meta-analyses, and ACO and asthma exacerbations in specific cohorts. Models were adjusted for confounders and genetic ancestry. Results: In meta-analyses of 102,477 participants, the PRSAsthma (odds ratio [OR] per SD, 1.16 [95% CI, 1.14-1.19]) and PRSspiro (OR per SD, 1.19 [95% CI, 1.17-1.22]) both predicted asthma, whereas the PRSspiro predicted COPD (OR per SD, 1.25 [95% CI, 1.21-1.30]). However, results differed by cohort. The PRSspiro was not associated with COPD in GERA and Mass General Brigham Biobank. In the Genetic Epidemiology of COPD study, the PRSAsthma (OR per SD: Whites, 1.3; African Americans, 1.2) and PRSspiro (OR per SD: Whites, 2.2; African Americans, 1.6) were both associated with ACO. In GERA, the PRSAsthma was associated with asthma exacerbations (OR, 1.18) in Whites; the PRSspiro was associated with asthma exacerbations in White, LatinX, and East Asian participants. Conclusions: PRSs for asthma and spirometry are both associated with ACO and asthma exacerbations. Genetic prediction performance differs in research versus electronic health record–based cohorts.
AB - Background: Asthma and chronic obstructive pulmonary disease (COPD) have distinct and overlapping genetic and clinical features. Objective: We sought to test the hypothesis that polygenic risk scores (PRSs) for asthma (PRSAsthma) and spirometry (FEV1 and FEV1/forced vital capacity; PRSspiro) would demonstrate differential associations with asthma, COPD, and asthma-COPD overlap (ACO). Methods: We developed and tested 2 asthma PRSs and applied the higher performing PRSAsthma and a previously published PRSspiro to research (Genetic Epidemiology of COPD study and Childhood Asthma Management Program, with spirometry) and electronic health record–based (Mass General Brigham Biobank and Genetic Epidemiology Research on Adult Health and Aging [GERA]) studies. We assessed the association of PRSs with COPD and asthma using modified random-effects and binary-effects meta-analyses, and ACO and asthma exacerbations in specific cohorts. Models were adjusted for confounders and genetic ancestry. Results: In meta-analyses of 102,477 participants, the PRSAsthma (odds ratio [OR] per SD, 1.16 [95% CI, 1.14-1.19]) and PRSspiro (OR per SD, 1.19 [95% CI, 1.17-1.22]) both predicted asthma, whereas the PRSspiro predicted COPD (OR per SD, 1.25 [95% CI, 1.21-1.30]). However, results differed by cohort. The PRSspiro was not associated with COPD in GERA and Mass General Brigham Biobank. In the Genetic Epidemiology of COPD study, the PRSAsthma (OR per SD: Whites, 1.3; African Americans, 1.2) and PRSspiro (OR per SD: Whites, 2.2; African Americans, 1.6) were both associated with ACO. In GERA, the PRSAsthma was associated with asthma exacerbations (OR, 1.18) in Whites; the PRSspiro was associated with asthma exacerbations in White, LatinX, and East Asian participants. Conclusions: PRSs for asthma and spirometry are both associated with ACO and asthma exacerbations. Genetic prediction performance differs in research versus electronic health record–based cohorts.
KW - Asthma
KW - asthma-COPD overlap
KW - chronic obstructive pulmonary disease
KW - heterogeneity
KW - polygenic risk scores
UR - https://www.scopus.com/pages/publications/85171135677
U2 - 10.1016/j.jaci.2023.08.002
DO - 10.1016/j.jaci.2023.08.002
M3 - Article
C2 - 37595761
SN - 0091-6749
VL - 152
SP - 1423
EP - 1432
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 6
ER -