Sex and Obesity Stratified Asthma GWAS in African and European Ancestry Populations
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
Biologically distinct asthma subgroups may obscure genetic effects when analyzed as a single phenotype. We examined whether asthma susceptibility signals are shared, heterogeneous, or stratum-specific across ancestry, obesity status, and sex.
Methods
We performed ancestry-specific GWAS meta-analyses in African ancestry participants (9,965 asthma cases; 37,391 controls) and European ancestry participants (6,074 cases; 116,255 controls), followed by obesity- and sex-stratified analyses. Analyses used imputed dosages and fixed-effect meta-analysis within ancestry.
Results
Stratification detected asthma association signals that were less apparent in the combined phenotype. Shared cross-ancestry loci implicated epithelial antiviral susceptibility and immune regulation, represented by signals near CDHR3 and FOXO1 . An ancestry-heterogeneous signal at the 17q21 locus, harboring ORMDL3 / GSDMB, supported population-dependent effects at an epithelial inflammatory locus. Obesity stratification mapped the genome-wide significant burden to asthma without obesity. Sex stratification detected genome-wide significant signals in AFR females with asthma and obesity and in both sex strata with asthma without obesity, with the strongest signal burden in EU females without obesity.
Conclusions
Asthma genetic architecture differed by ancestry, obesity status, and sex. Stratified analyses identified group-specific susceptibility related to epithelial and immune regulation, airway inflammation, remodeling, and neural signaling, supporting precision approaches to asthma.
