Exploring the shared genetic architecture between post-traumatic stress disorder (PTSD) and obstructive sleep apnea (OSA)
TL;DR
A shared genetic basis of PTSD and OSA is revealed, characterised by genetic correlation, shared novel variants, tissue enrichment, and causal relationships, providing evidence for genetic overlap underlying their biological mechanisms.
Abstract
ABSTRACT 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 rg = 0.336 (constrained-intercept LDSC, p = 2.56 × 10−⁴⁴) and rg = 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.