We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 cases, 118,538 controls) from ethnically-diverse populations. We identified five new asthma loci, uncovered two additional novel associations at two known asthma loci, established asthma associations at two loci implicated previously in comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. Enrichment of asthma risk loci in enhancer marks, especially in immune cells, suggests a major role of these loci in the regulation of immune-related mechanisms.

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What does this study add to the field?Using latent class analysis (LCA), we identified two subgroups among a cohort of 483 patients with COVID-19-related ARDS. Class 2 patients had higher inflammatory markers and lactate and corresponded with the previously identified hyperinflammatory subphenotype, whereas Class 1 corresponded with the hypoinflammatory subphenotype. Class 2 had significantly higher 90-day mortality compared with Class 1 (75% vs 48%; p<0•0001). Differential response to corticosteroid treatment was observed, with decreased mortality in steroid-treated patients in Class 2 but not Class 1. SARS-CoV-2 polymerase chain reaction cycle threshold was a predictor of mortality in Class 1, but not Class 2, suggesting distinct drivers of mortality among classes.

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