Investigating the shared genetic architecture between obstructive sleep apnea and sleep‐related traits

Abstract

Abstract Background Despite a strong link between obstructive sleep apnea (OSA) and sleep traits, the shared genetic architecture remains unclear. This study aims to explore the shared genetic basis and bidirectional causal between OSA and sleep traits. Methods Using large‐scale genome‐wide association studies summary statistics for OSA and sleep traits, we employed linkage disequilibrium score regression (LDSR) and MiXeR to examine genetic correlations and quantify polygenic overlaps. The causal association was explored by bidirectional Mendelian randomization. In addition, we identified shared genomic loci through conditional and conjunctional false discovery rate (cond/conjFDR) analysis, followed by annotation to identify shared genes. Finally, we performed enrichment, developmental trajectory, and phenome‐wide association study analysis of the shared genes to explore underlying mechanisms. Results We found that both LDSR and MiXeR results revealed substantial genetic correlations and polygenic overlaps between OSA and most of sleep traits. MR analysis supported bidirectional causality between OSA and sleep traits such as insomnia and snoring. Subsequent conjFDR analysis pinpointed 168 distinct shared loci, which encompassed 695 unique genes, and these genes are predominantly enriched in the neurodevelopmental and metabolic process pathways. Notably, the expression of 38 shared genes exhibits a significant correlation with both OSA and sleep traits. These shared genes exhibit specific developmental trajectories and demonstrate significant pleiotropic associations with phenotypes such as metabolism, immunity, and brain structure. Conclusion This study uncovers the broad pleiotropy of the genetic architecture shared between OSA and sleep traits, highlighting neurodevelopmental and metabolic pathways as the key shared biological underpinnings.