Common Heritable Contributions to Low-Risk Trauma, High-Risk Trauma, Posttraumatic Stress Disorder, and Major Depression

Abstract

Context Understanding the relative contributions of genetic and environmental factors to trauma exposure, post-traumatic stress disorder (PTSD), and major depressive disorder (MDD) is critical to developing etiologic models of these conditions and their co-occurrence. Objectives To quantify heritable influences on low-risk trauma, high-risk trauma, PTSD, and MDD and to estimate the degree of overlap between genetic and environmental sources of variance in these 4 phenotypes. Design Adult twins and their siblings were ascertained from a large population-based sample of female and male twin pairs on the basis of screening items for childhood sexual abuse and physical abuse obtained in a previous assessment of this cohort. Setting Structured psychiatric telephone interviews. Participants Total sample size of 2591: 996 female and 536 male twins; 625 female and 434 male nontwin siblings. Main Outcome Measure Lifetime low- and high-risk trauma exposure, PTSD, and MDD. Results In the best-fitting genetic model, 47% of the variance in low-risk trauma exposure and 60% of the variance in high-risk trauma exposure was attributable to additive genetic factors. Heritable influences accounted for 46% of the variance in PTSD and 27% of the variance in MDD. An extremely high degree of genetic overlap was observed between high-risk trauma exposure and both PTSD (r =0.89; 95% CI, 0.78-0.99) and MDD (r =0.89; 95% CI, 0.77-0.98). Complete correlation of genetic factors contributing to PTSD and to MDD (r=1.00) was observed. Conclusions The evidence suggests that almost all the heritable influences on high-risk trauma exposure, PTSD, and MDD, can be traced to the same sources; that is, genetic risk is not disorder specific. Individuals with a positive family history of either PTSD or MDD are at elevated risk for both disorders and should be closely monitored after a traumatic experience for symptoms of PTSD and MDD.

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

“…Interestingly, this genetic correlation declined as the number of assaultive traumas reached high levels, consistent with the hypothesis that large doses of trauma can cause PTSD regardless of genetic vulnerability (Jang et al, 2007). In a large populationbased twin sample in which the heritability of PTSD was 0.46, even larger estimates were observed for the heritability of high-risk trauma (h 2 = 0.60), and the genetic correlation between high-risk trauma and PTSD was again substantial (r g = 0.89) (Sartor et al, 2012).…”

“…For example, in twin samples, genetic variation underlying the risk of MDD and GAD overlaps completely (Kendler et al, 2007;Roy et al, 1995). Significant genetic correlations have also been reported between MDD and, respectively, PTSD (0.77-1.0), BPD (0.65), alcohol dependence (0.40-0.60), ADHD (0.67-0.77), and nicotine dependence (0.21), and neuroticism (0.43) (Cole et al, 2009;Edwards and Kendler, 2012;Kendler et al, 1993a;Kendler and Myers, 2010;Koenen et al, 2008Koenen et al, , 2003McGuffin et al, 2003;Sartor et al, 2012). Anxiety symptoms and ADHD symptoms also show substantial genetic correlations (0.45-0.58) (Michelini et al, 2015).…”

Genetic Association Analysis of 300 Genes Identifies a Risk Haplotype in SLC18A2 for Post-traumatic Stress Disorder in Two Independent Samples

“…PTSD is highly comorbid with other psychiatric disorders (Breslau, 2002) and twin studies suggest that this comorbidity is at least partially explained by common genetic influences. In particular, genetic influences common to MDD account for the majority of the genetic variance in PTSD (Sartor et al, 2012;Wolf et al, 2010). Analyses of the structure of common mental disorders suggest PTSD loads with MDD on a common internalizing 'distress' or 'anxiousmisery' factor (Cox et al, 2002;Slade and Watson, 2006).…”

“…The SNPs in our study were chosen to comprehensively cover candidate genes in the literature as well as top hits from published genome-wide association studies (GWAS) of psychiatric disorders. Since twin studies suggest PTSD has a high genetic overlap with other psychiatric disorders, particularly with major depression (Sartor et al, 2012;Wolf et al, 2010), we also conducted polygenic analyses using results for bipolar disorder (BP), major depressive depression (MDD), and schizophrenia (SZ) from the Psychiatric Genome-Wide Association Studies Consortium (PGC) (2012b; Ripke et al, 2011;Sklar et al, 2011). We found a significant association between PTSD diagnosis and SLC18A2 after correction for multiple testing.…”

Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene

“…A large proportion of the genetic liability for PTSD is also shared with other mental disorders such as anxiety and panic disorder (Goenjian et al, 2008), major depressive disorder (MDD) (Fu et al, 2007;Sartor et al, 2012), and substance use (Xian et al, 2000), hence genes that confer risk for PTSD may also influence risk for other psychiatric disorders and vice versa (Nugent et al, 2008). Such pleiotropic effects have been demonstrated across several psychiatric disorders (Solovieff et al, 2013).…”