Response to: Further Support for an Association between the Memory-Related Gene WWC1 and Posttraumatic Stress Disorder: Results from the Detroit Neighborhood Health Study

Abstract

P osttraumatic stress disorder (PTSD) is characterized by pathologic, intrusive memories of the experienced traumata. The risk to develop PTSD depends on the cumulative exposure to traumatic experience (traumatic load), on the extent of childhood adversities, and on genetic factors. The latter account for about one third of interindividual variability (1). Despite this pronounced genetic influence, little is known about the underlying genetic factors and molecular processes. Considering the strong role of fear memory development in PTSD, we recently argued for the investigation of memory-related genes in PTSD (2,3). Candidate gene association studies allow for such theorydriven analyses; however, they require replication to identify reliable associations between molecular genetic factors and PTSD.The gene encoding the protein KIBRA (WWC1) is reliably associated with human episodic memory (4,5) and accumulating evidence from three independent samples now suggests a role of this gene in PTSD etiology. We discovered that WWC1 genotype influenced PTSD risk in a sample of Rwandan genocide survivors and replicated this finding in a second study with survivors of the rebel war in Northern Uganda (6). Minor-allele carrier status of two WWC1 single nucleotide polymorphisms (SNPs) (rs10038727 and rs4576167) was associated with decreased risk for lifetime PTSD development, an effect that held true for all levels of traumatic load. Our results on rs10038727 were replicated by Sumner et al. (7), who examined a large, predominantly African American sample from the Detroit Neighborhood Health Study. The authors also included a measure of lifetime trauma exposure and found a strong main effect of trauma. However, neither in this study nor in our study was a gene  environment (traumatic load) interaction effect observed.The accumulating evidence for the relevance of WWC1 genotype for both human memory and memory-related psychopathology brings up several research questions.