This is the first study to compare heritability of binary (diagnostic) and continuous (symptom-based) phenotypes for PTSD directly. Although PTSD symptoms can have a very diverse phenotypic presentation14, their genetic overlap is very high (rg > 0.9). This is an important novel insight into the biology of PTSD. The quantitative (PCL-Total) trait – which reflected the most information – was the most heritable, and therefore the most informative for biological inference. Partitioned heritability analyses of that trait indicated overrepresentation of SNPs in frontal (BA9) and anterior cingulate cortex (BA24), consistent with prevailing neural circuit theories of PTSD pathophysiology2 that emphasize hypofunction of these regions and their connections with limbic cortex in the regulation of emotion and extinction of fear memories48,49. However, these analyses also pointed to the nucleus accumbens – an important component of the reward system – as being involved in PTSD symptoms. These results suggest that more extensive study of the nucleus accumbens and reward systems in PTSD may shed further light on aspects of the syndrome (e.g., its strong association with alcohol dependence)50,51 that are currently not well understood.
