The following is a summary of “Polygenic risk scores identify heterogeneity in asthma and chronic obstructive pulmonary disease,” published in the DECEMBER 2023 issue of Allergy & Immunology by Moll, et al.

Asthma and chronic obstructive pulmonary disease (COPD) exhibit distinct yet overlapping genetic and clinical features. For a study, researchers sought to test the hypothesis that polygenic risk scores (PRSs) for asthma (PRS_Asthma) and spirometry (FEV₁ and FEV₁/forced vital capacity; PRS_spiro) would demonstrate differential associations with asthma, COPD, and asthma-COPD overlap (ACO).

The study developed and tested two asthma PRSs and applied the higher-performing PRSAsthma and a previously published PRSspiro to research studies (Genetic Epidemiology of COPD study and Childhood Asthma Management Program) and electronic health record–based studies (Mass General Brigham Biobank and Genetic Epidemiology Research on Adult Health and Aging [GERA]). The association of PRSs with COPD and asthma was assessed using meta-analyses and binary-effects meta-analyses. Models were adjusted for confounders and genetic ancestry.

In meta-analyses of 102,477 participants, both PRS_Asthma (odds ratio [OR] per SD, 1.16 [95% CI, 1.14-1.19]) and PRS_spiro (OR per SD, 1.19 [95% CI, 1.17-1.22]) predicted asthma. The PRSspiro also predicted COPD (OR per SD, 1.25 [95% CI, 1.21-1.30]). However, results varied by cohort. The PRS_spiro was not associated with COPD in GERA and Mass General Brigham Biobank. In the Genetic Epidemiology of COPD study, both PRS_Asthma and PRS_spiro were associated with ACO. In GERA, PRS_Asthma was associated with asthma exacerbations (OR, 1.18) in Whites; PRS_spiro was associated with asthma exacerbations in White, LatinX, and East Asian participants.

PRSs for asthma and spirometry are associated with ACO and asthma exacerbations. Genetic prediction performance differs in research versus electronic health record–based cohorts.

Source: jacionline.org/article/S0091-6749(23)00988-0/fulltext