Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - The Role of Memory-related Gene WWC1 (KIBRA) in Lifetime Posttraumatic Stress Disorder
T2 - Evidence from Two Independent Samples from African Conflict Regions
AU - Wilker, Sarah
AU - Kolassa, Stephan
AU - Vogler, Christian
AU - Lingenfelder, Birke
AU - Elbert, Thomas
AU - Papassotiropoulos, Andreas
AU - de Quervain, Dominique J.-F.
AU - Kolassa, Iris-Tatjana
PY - 2013/11/1
Y1 - 2013/11/1
N2 - Background Posttraumatic stress disorder (PTSD) results from the formation of a strong memory for the sensory-perceptual and affective representations of traumatic experiences, which is detached from the corresponding autobiographical context information. Because WWC1, the gene encoding protein KIBRA, is associated with long-term memory performance, we hypothesized that common WWC1 alleles influence the risk for a lifetime diagnosis of PTSD. Methods Traumatic load and diagnosis of current and lifetime PTSD were assessed in two independent African samples of survivors from conflict zones who had faced severe trauma (n = 392, Rwanda, and n = 399, Northern Uganda, respectively). Array-based single nucleotide polymorphism (SNP) genotyping was performed. The influence of WWC1 tagging SNPs and traumatic load on lifetime PTSD was estimated by means of logistic regression models with correction for multiple comparisons in the Rwandan sample. Replication analysis was performed in the independent Ugandan sample. Results An association of two neighboring SNPs in almost complete linkage disequilibrium, rs10038727 and rs4576167, with lifetime PTSD was discovered in the Rwandan sample. Although each traumatic event added to the probability of lifetime PTSD in a dose-dependent manner in both genotype groups, carriers of the minor allele of both SNPs displayed a diminished risk (p = .007, odds ratio = .29 [95% confidence interval = .15–.54]). This effect was confirmed in the independent Ugandan sample. Conclusions This study reveals an association between two WWC1 SNPs and the likelihood of PTSD development, indicating that this memory-related gene might be involved in processes that occur in response to traumatic stress and influence the strengthening of fear memories.
AB - Background Posttraumatic stress disorder (PTSD) results from the formation of a strong memory for the sensory-perceptual and affective representations of traumatic experiences, which is detached from the corresponding autobiographical context information. Because WWC1, the gene encoding protein KIBRA, is associated with long-term memory performance, we hypothesized that common WWC1 alleles influence the risk for a lifetime diagnosis of PTSD. Methods Traumatic load and diagnosis of current and lifetime PTSD were assessed in two independent African samples of survivors from conflict zones who had faced severe trauma (n = 392, Rwanda, and n = 399, Northern Uganda, respectively). Array-based single nucleotide polymorphism (SNP) genotyping was performed. The influence of WWC1 tagging SNPs and traumatic load on lifetime PTSD was estimated by means of logistic regression models with correction for multiple comparisons in the Rwandan sample. Replication analysis was performed in the independent Ugandan sample. Results An association of two neighboring SNPs in almost complete linkage disequilibrium, rs10038727 and rs4576167, with lifetime PTSD was discovered in the Rwandan sample. Although each traumatic event added to the probability of lifetime PTSD in a dose-dependent manner in both genotype groups, carriers of the minor allele of both SNPs displayed a diminished risk (p = .007, odds ratio = .29 [95% confidence interval = .15–.54]). This effect was confirmed in the independent Ugandan sample. Conclusions This study reveals an association between two WWC1 SNPs and the likelihood of PTSD development, indicating that this memory-related gene might be involved in processes that occur in response to traumatic stress and influence the strengthening of fear memories.
KW - Genetics
KW - memory
KW - posttraumatic stress disorder
KW - risk
KW - trauma
U2 - 10.1016/j.biopsych.2013.02.022
DO - 10.1016/j.biopsych.2013.02.022
M3 - Journal article
VL - 74
SP - 664
EP - 671
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 9
ER -