Wanqing Lin,1,2,* Zhiyi Zhang,3,* Chenlin Wang,4 Yingling Ye,4 Lingrong Zheng,4 Qianqian Hu,4 Renyu Yu,1 Mingxia Wu,4,5 Bin Chen1 

1Department of Rehabilitation Medicine and National Clinical Research Base of Traditional Chinese Medicine, The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, 350004, People’s Republic of China; 2Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, 350003, People’s Republic of China; 3Department of Massage, Quanzhou Orthopedic-Traumatological Hospital, Quanzhou, Fujian Province, 362000, People’s Republic of China; 4Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, 350122, People’s Republic of China; 5Second People’s Hospital Affiliated to Fujian University of Chinese Medicine, Fuzhou, Fujian Province, 350001, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Mingxia Wu; Bin Chen, Email wumingxiafz@163.com; chenbin327425224@163.com

Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.

Keywords: obstructive sleep apnea, ischemic stroke, GWAS, genetic overlap