Genetic correlation and causality assessment between post-traumatic stress disorder and coronary artery disease-related traits

Abstract

Consistent evidence from observational studies supports a risk-increasing association between post-traumatic stress disorder (PTSD) and coronary artery disease (CAD); however, the mechanisms underlying their relationship remain poorly understood. This study assesses the genetic correlation and potential causal relationship between PTSD and CAD-related traits. We analysed genome-wide associated study summary data of PTSD (cases = 23,212, controls = 151,447) with CAD-related traits (sample size up to 408,458 individuals) to achieve our study objectives. Findings revealed a significant and positive genetic correlation between PTSD and CAD (rG = 0.19, p = 3.47 × 10–2), and between PTSD and CAD traits of ischemic heart disease (genetic correlation [rG] = 0.42, p = 5.17 × 10–10), coronary arteriosclerosis (rG = 0.32, p = 3.78 × 10–7), and angina pectoris (rG = 0.48, p = 1.14 × 10–9). However, Mendelian randomisation (MR) analysis found no evidence for a significant causal association between PTSD and CAD traits, regardless of analysis direction (PTSD or CAD traits as the exposure or outcome variable). Findings from MR sensitivity analyses were consistent, suggesting that genetic liability to PTSD has no causal influence on any CAD trait and vice versa. In summary, our study provides evidence implicating a positive genetic correlation between PTSD with CAD-related traits, supporting evidence of a risk-increasing but non-causal association between them.