Shared Genetic Risk Between Cardiovascular Disease and PTSD

Cardiovascular disease (CVD) and posttraumatic stress disorder (PTSD) may share genetic risk, and PTSD may also be a risk factor for coronary artery disease (CAD) and hypertension, according to study findings published in The American Journal of Psychiatry.

Researchers conducted a meta-analysis, genome-wide cross-trait analysis, and Mendelian randomization analyses that included more than 36,400 participants from the Mass General Brigham Biobank (MGBB), a biorepository of Massachusetts General Hospital (Boston MA), and McLean Hospital (Belmont, MA). Illumina single nucleotide polymorphism array was used to genotype de-identified genetic data from the biobank as of April 2020. At least 1 ICD-10 code determined the diagnosis of PTSD, and algorithms developed by MGBB determined hypertension and depression phenotypes from already curated disease populations.

A total of 2149 participants PTSD-positive and 34,269 PTSD-negative control participants were included in the study. They noted 6167 participants with major depressive disorder (MDD) or past history of MDD, of whom 1133 had comorbid PTSD, and the 30,243 remaining participants did not have MDD.

Researchers used individual genome-wide association study summary statistics to calculate initial estimates, then calculated large scale meta-analysis summary statistics by combining MGBB summary statistics with publicly available data. They found significant positive genetic correlations between CAD and PTSD (r_G=0.24, SE=0.06). Significant positive genetic correlations between hypertension and PTSD were also observed (r_G=0.35, SE=0.06).

There were significant genetic correlations between MDD and hypertension (r_G=0.31, SE=0.03) as well as MDD and CAD (r_G=0.18, SE=0.03).

Researchers noted a potential causal link from PTSD to hypertension (β=0.20, SE=0.04), but not a reverse link from hypertension to PTSD as indicated in Mendelian randomization analyses. PTSD significantly predicted CAD (β=0.22, SE=0.07), MDD significantly predicted hypertension (β=0.43, SE=0.10), and MDD significantly predicted CAD (β=0.47, SE=0.14).

PTSD diagnostic status was significantly predicted by PTSD summary statistics (R²=0.27), and improved by integrating CVD and major depressive disorder summary statistics (R²=1.30). It was noted that genetic variants involved in shared CVD-PTSD risk included those involved in synapse organization, postsynaptic structure, and interleukin-7-mediated signaling pathways as indicated by pathway enrichment analysis.

Limitations of the study include basing PTSD diagnosis on single ICD-10 codes, the inclusion of primarily White non-Hispanic participants, and the lack of data on behavioral variables that likely influence the pathways of PTSD leading to CVD.

Study authors concluded, “We identified significant genetic correlations between PTSD and CVD….We were also able to significantly improve the genetic prediction of PTSD by incorporating summary statistics from CVD and MDD.” They added, “[G]enetic variants involved in shared PTSD-CVD risk included those involved in postsynaptic structure, synapse organization, and immune function.”

Disclosure: One study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.