Multi-ancestry meta-analysis of asthma identifies novel associations and highlights the value of increased power and diversity.

Asthma is a complex disease that varies widely in prevalence across populations. The extent to which genetic variation contributes to these disparities is unclear, as the genetics underlying asthma have been investigated primarily in populations of European descent. As part of the Global Biobank Meta-analysis Initiative, we conducted a large-scale genome-wide association study of asthma (153,763 cases and 1,647,022 controls) via meta-analysis across 22 biobanks spanning multiple ancestries. We discovered 179 asthma-associated loci, 49 of which were not previously reported. Despite the wide range in asthma prevalence among biobanks, we found largely consistent genetic effects across biobanks and ancestries. The meta-analysis also improved polygenic risk prediction in non-European populations compared with previous studies. Additionally, we found considerable genetic overlap between age-of-onset subtypes and between asthma and comorbid diseases. Our work underscores the multi-factorial nature of asthma development and offers insight into its shared genetic architecture.

5,051 African ancestry cases, 27,607 African ancestry controls, 4,069 Hispanic or Latin American cases, 14,104 Hispanic or Latin American controls, 4,015 Central Asian ancestry cases, 27,091 Central Asian ancestry controls, 4,015 South Asian ancestry cases, 27,091 South Asian ancestry controls, 18,549 East Asian ancestry cases, 322,655 East Asian ancestry controls, 121,940 European ancestry cases, 1,254,131 European ancestry controls, 139 Greater Middle Eastern (Middle Eastern, North African or Persian) cases, 1,434 Greater Middle Eastern (Middle Eastern, North African or Persian) controls