Genomic Correlations, Shared Loci, and Drug Targets Between Polycystic Ovary Syndrome and Asthma: Insights From Genome-wide Association Analysis.

BACKGROUND

Observational studies have shown an association between polycystic ovary syndrome (PCOS) and asthma-related traits. However, whether this association is genetically driven or arises from observational biases remains unclear.

METHODS

This study integrated data from 10 074 PCOS cases and asthma-related traits obtained from the UK Biobank and FinnGen cohorts. Global and local genetic architectures were examined using pleiotropic analysis under the composite null hypothesis, functional mapping and annotation of genetic associations, and fine-mapping credible set analysis. Drug database mining was employed to identify pleiotropic genes as potential therapeutic targets. Tissue and cell enrichment analyses were conducted to uncover shared biological mechanisms.

RESULTS

We identified 3 novel significant genetic loci for asthma subtypes (2 for allergic asthma and 1 for childhood asthma). A positive overall genetic correlation between PCOS and asthma-related traits was observed. We discovered 5 pleiotropic causal regions encompassing 13 genes, with ERBB3 emerging as a potential central gene contributing to the shared pathophysiology of PCOS and asthma-related traits. Additionally, drug repositioning analysis suggested anakinra and artenimol as potential therapeutic candidates for PCOS and asthma comorbidity. The linkage disequilibrium score for the specific expression of genes analysis, along with transcriptome-wide association studies, further identified gene expression patterns at the tissue/cell level in the hypothalamo-pituitary, exocrine/endocrine, respiratory, and urogenital systems.

CONCLUSION

Our findings provide novel insights into the genetic basis and biological processes underlying the association between PCOS and asthma-related traits, warranting evaluation of whether PCOS-specific asthma risk assessment could improve clinical outcomes.