Genetic Overlap Between Obstructive Sleep Apnea and Ischemic Stroke: A Large-Scale Genome-Wide Cross-Trait Analysis

To further understand the complex relationship between Obstructive Sleep Apnea (OSA) and ischemic stroke, this study explores the role of genetic factors in the comorbidity of these two conditions.

Based on large-scale available Genome-Wide Association Studies (GWAS) for OSA and ischemic stroke, we conducted a multi-level cross-trait analysis. First, we utilized Linkage Disequilibrium Score Regression (LDSC) to analyze the genetic correlation between the two diseases. Subsequently, we performed cross-trait analysis to identify pleiotropic Single Nucleotide Polymorphisms (SNPs) associated with both OSA and ischemic stroke. On this basis, we applied annotation and Multi-marker Analysis of GenoMic Annotation (MAGMA) analysis to examine results at the gene level. Finally, we conducted Transcriptome-Wide Association Studies (TWAS) to analyze gene expressions significantly related to both traits.

The LDSC analysis revealed a significant positive genetic correlation between OSA and ischemic stroke. Cross-trait analysis identified a total of 90 pleiotropic SNPs, with rs78581380 being the most significant. Combining Functional Mapping and Annotation (FUMA) annotation and MAGMA analysis, we identified 83 genes in total. TWAS analysis discovered 23 gene expressions that were significantly associated with both OSA and ischemic stroke traits.

This study elucidates the shared genetic architecture between OSA and ischemic stroke, emphasizing the crucial role of genetic factors in the comorbidity of these two conditions.