Shared Genetic Architecture of Obstructive Sleep Apnea and Neck Pain: A Large-Scale Genome-Wide Association Study

This study aims to explore the role of genetic factors in the co-occurrence of neck pain and obstructive sleep apnea (OSA), thereby providing a deeper understanding of their intrinsic relationship.

We analyzed GWAS data for OSA from the FinnGen consortium (38,998 cases and 336,659 controls), and neck pain from the UK Biobank (106,521 cases and 355,336 controls), all of European ancestry. Genetic correlation between neck pain and OSA using the Linkage Disequilibrium Score Regression (LDSC) method and High-definition Likelihood (HDL) method. Local correlation was examined across 2,795 loci with Local Analysis of Variant Association (LAVA). Mendelian randomization (MR) was conducted to infer causality. Cross-Phenotype Association (CPASSOC) identified pleiotropic SNPs, which were annotated with FUMA and validated by MAGMA. Transcriptome-wide association study (TWAS) and tissue enrichment analyses were further applied to explore biological mechanisms.

MR analysis indicated that NP increases the risk of OSA. CPASSOC identified 150 pleiotropic SNPs, with 40 loci annotated by FUMA, yielding 85 pleiotropic genes consistent with MAGMA. TWAS highlighted seven genes with significant pleiotropic effects on both NP and OSA. Tissue enrichment revealed that pleiotropic gene expression was predominantly localized in brain tissues, particularly the cerebral cortex (P=2.17E-6). These genes suggested involvement of neurodevelopmental and metabolic pathways in neck pain-OSA comorbidity. In MR,we found that individuals with neck pain had an increased risk of developing OSA.

Our findings underscore the pivotal role of genetic factors in neck pain-OSA comorbidity and provide theoretical support for considering pain management as part of clinical strategies for OSA.