Exploring the shared genetic architecture between post-traumatic stress disorder (PTSD) and obstructive sleep apnea...

Background: Observational research has revealed an association between post-traumatic stress disorder (PTSD) and obstructive sleep apnea (OSA), but their shared genetic architecture remains unclear. This study aimed to characterise their shared genetic architecture and evaluate potential causal relationships.Methods: Genome-wide association study (GWAS) summary statistics for PTSD and OSA were analyzed. Genetic correlations were estimated using linkage disequilibrium score regression (LDSC). Cross-trait meta-analyses were applied to explore pleiotropic loci, and Bayesian colocalization was performed to identify shared causal variants. Tissue enrichment and gene-level associations were evaluated using stratified LDSC and Multi-marker Analysis of Genomic Annotation (MAGMA). Bidirectional causality was tested with two-sample Mendelian randomization (MR). Transcriptome-wide association studies (TWAS) were used to identify shared gene expression patterns across enriched tissues.Results: Significant global genetic correlations were found between PTSD and OSA, with r_g = 0.336 (constrained-intercept LDSC, p = 2.56 × 10^-⁴⁴) and r_g = 0.301 (unconstrained LDSC, p = 5.47 × 10^-¹¹³). Cross-trait meta-analyses identified 12 novel pleiotropic SNPs with concordant effect directions across traits. Colocalization detected two shared causal loci with high posterior probabilities: TRAF3 at 9q33.3 (PP.H4 = 96.35%) and TMEM106B at 7p21.3 (PP.H4 = 95.63%). Tissue-specific SNP heritability enrichment was observed in the cerebellum, cerebellar hemisphere, and cortex. MR showed that genetically predicted PTSD was significantly associated with increased risk of OSA (IVW OR = 3.24, 95% CI: 2.42-4.34, p = 2.84 × 10^-15), while no significant reverse causal effect was observed. TWAS consistently identified TRIM72, VDAC2P4, EFCAB5, and NSRP1 across the cerebellum, cerebellar hemisphere, and cortex.Conclusion: This study reveals a shared genetic basis of PTSD and OSA, characterised by genetic correlation, shared novel variants, tissue enrichment, and causal relationships, providing evidence for genetic overlap underlying their biological mechanisms.