Experiencing a traumatic event may lead to Posttraumatic Stress Disorder (PTSD), including symptoms such as flashbacks and hyperarousal. Individuals suffering from PTSD are at increased risk of cardiovascular disease (CVD), but it is unclear why. This study assesses shared genetic liability and potential causal pathways between PTSD and CVD. We leveraged summary-level data of genome-wide association studies (PTSD: N = 1,222,882
atrial fibrillation (AF): N = 482,409
coronary artery disease (CAD): N = 1,165,690
hypertension (HT): N = 458,554
heart failure (HF): N = 977,323). First, we estimated genetic correlations and utilized genomic structural equation modeling to identify a common genetic factor for PTSD and CVD. Next, we assessed biological, behavioural, and psychosocial factors as potential mediators. Finally, we employed multivariable Mendelian randomization to examine causal pathways between PTSD and CVD, incorporating the same potential mediators. Significant genetic correlations were found between PTSD and CAD, HT, and HF (r