Leveraging large-scale genetics of PTSD and cardiovascular disease demonstrates robust shared risk and improves risk prediction accuracy

Individuals with posttraumatic stress disorder (PTSD) are significantly more likely to be diagnosed with cardiovascular disease (CVD; e.g., myocardial infarction, stroke). The evidence for this link is so compelling that the National Institutes of Health convened a working group to determine gaps in the current literature, including the need for large-scale genomic studies to identify shared genetic risk. The current study used a large healthcare biobank dataset of N = 36,412 individuals, combined with GWAS summary statistics from publicly available, large-scale PTSD and CVD studies. We found significant genetic correlations between PTSD and CVD (r G =0.24, S.E.= 0.05982, p=5 . 09E-05 ), and Mendelian randomization analyses indicated a potential causal link from PTSD to hypertension ( β =0.20, S.E.= 0.04, p=5 . 97e-6 ), but not the reverse. PTSD summary statistics significantly predicted PTSD diagnostic status ( R 2 =0.27%, p = 5 . 31E-08 ), and this was significantly improved by incorporating summary statistics from CVD and major depressive disorder ( R 2 =1.30%, p = 2 . 16E-32 ). Further, pathway enrichment analyses indicated that genetic variants involved in shared PTSD-CVD risk included those involved in postsynaptic structure ( p=0 . 00001 ), synapse organization ( p=0 . 0001 ), and interleukin-7 (IL-7) mediated signaling pathways ( p=0 . 0002 ). While additional research is needed to determine the clinical utility of these findings, these data further support the biological shared risk for stress-related disorders of mental health and cardiovascular illness.