TY - JOUR
T1 - Attachment Style Moderates Polygenic Risk for Posttraumatic Stress in United States Military Veterans
T2 - Results From the National Health and Resilience in Veterans Study
AU - Tamman, Amanda J.F.
AU - Wendt, Frank R.
AU - Pathak, Gita A.
AU - Krystal, John H.
AU - Montalvo-Ortiz, Janitza L.
AU - Southwick, Steven M.
AU - Sippel, Lauren M.
AU - Gelernter, Joel
AU - Polimanti, Renato
AU - Pietrzak, Robert H.
N1 - Publisher Copyright:
© 2020 Society of Biological Psychiatry
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Background: A polygenic risk score (PRS) derived from genome-wide association studies of posttraumatic stress disorder (PTSD) may inform risk for this disorder. To date, however, no known study has examined whether social environmental factors such as attachment style may moderate the relation between PRS and PTSD. Methods: We evaluated main and interactive effects of PRS and attachment style on PTSD symptoms in a nationally representative sample of trauma-exposed European-American U.S. military veterans (N = 2030). PRS was derived from a genome-wide association study of PTSD re-experiencing symptoms (N = 146,660) in the Million Veteran Program cohort. Using one-sample Mendelian randomization with data from the UK Biobank (N = 115,099), we evaluated the effects of re-experiencing PRS and attachment style on PTSD symptoms. Results: Higher re-experiencing PRS and secure attachment style were independently associated with PTSD symptoms. A significant PRS-by-attachment style interaction was also observed (β = −.11, p = .006), with a positive association between re-experiencing PRS and PTSD symptoms observed only among veterans with an insecure attachment style. One-sample Mendelian randomization analyses suggested that the association between PTSD symptoms and attachment style is bidirectional. PRS enrichment analyses revealed a significant interaction between attachment style and a variant mapping to the IGSF11 gene (rs151177743, p = 2.1 × 10−7), which is implicated in regulating excitatory synaptic transmission and plasticity. Conclusions: Attachment style may moderate polygenic risk for PTSD symptoms, and a novel locus implicated in synaptic transmission and plasticity may serve as a possible biological mediator of this association. These findings may help inform interpersonally oriented treatments for PTSD for individuals with high polygenic risk for this disorder.
AB - Background: A polygenic risk score (PRS) derived from genome-wide association studies of posttraumatic stress disorder (PTSD) may inform risk for this disorder. To date, however, no known study has examined whether social environmental factors such as attachment style may moderate the relation between PRS and PTSD. Methods: We evaluated main and interactive effects of PRS and attachment style on PTSD symptoms in a nationally representative sample of trauma-exposed European-American U.S. military veterans (N = 2030). PRS was derived from a genome-wide association study of PTSD re-experiencing symptoms (N = 146,660) in the Million Veteran Program cohort. Using one-sample Mendelian randomization with data from the UK Biobank (N = 115,099), we evaluated the effects of re-experiencing PRS and attachment style on PTSD symptoms. Results: Higher re-experiencing PRS and secure attachment style were independently associated with PTSD symptoms. A significant PRS-by-attachment style interaction was also observed (β = −.11, p = .006), with a positive association between re-experiencing PRS and PTSD symptoms observed only among veterans with an insecure attachment style. One-sample Mendelian randomization analyses suggested that the association between PTSD symptoms and attachment style is bidirectional. PRS enrichment analyses revealed a significant interaction between attachment style and a variant mapping to the IGSF11 gene (rs151177743, p = 2.1 × 10−7), which is implicated in regulating excitatory synaptic transmission and plasticity. Conclusions: Attachment style may moderate polygenic risk for PTSD symptoms, and a novel locus implicated in synaptic transmission and plasticity may serve as a possible biological mediator of this association. These findings may help inform interpersonally oriented treatments for PTSD for individuals with high polygenic risk for this disorder.
KW - Attachment style
KW - Gene enrichment
KW - Polygenic risk
KW - Posttraumatic stress disorder
UR - http://www.scopus.com/inward/record.url?scp=85097072118&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2020.09.018
DO - 10.1016/j.biopsych.2020.09.018
M3 - Article
C2 - 33276944
AN - SCOPUS:85097072118
SN - 0006-3223
VL - 89
SP - 878
EP - 887
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 9
ER -