Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers

R. Polimanti, J. Kaufman, H. Zhao, H. R. Kranzler, R. J. Ursano, R. C. Kessler, M. B. Stein, J. Gelernter

Research output: Contribution to journalArticlepeer-review


Objective: To investigate whether trauma exposure moderates the genetic correlation between substance use disorders and psychiatric disorders, we tested whether trauma exposure modifies the association of genetic risks for mental disorders with alcohol misuse and nicotine dependence (ND) symptoms. Methods: High-resolution polygenic risk scores (PRSs) were calculated for 10 732 US Army soldiers (8346 trauma-exposed and 2386 trauma-unexposed) based on genome-wide association studies of bipolar disorder (BD), major depressive disorder, and schizophrenia. Results: The main finding was a significant BD PRS-by-trauma interaction with respect to alcohol misuse (P = 6.07 × 10−3). We observed a positive correlation between BD PRS and alcohol misuse in trauma-exposed soldiers (r = 0.029, P = 7.5 × 10−3) and a negative correlation in trauma-unexposed soldiers (r = −0.071, P = 5.61 × 10−4). Consistent (nominally significant) result with concordant effect, directions were observed in the schizophrenia PRS-by-trauma interaction analysis. The variants included in the BD PRS-by-trauma interaction showed significant enrichments for gene ontologies related to high voltage-gated calcium channel activity (GO:0008331, P = 1.51 × 10−5; GO:1990454, P = 4.49 × 10−6; GO:0030315, P = 2.07 × 10−6) and for Beta1/Beta2 adrenergic receptor signaling pathways (P = 2.61 × 10−4). Conclusions: These results indicate that the genetic overlap between alcohol misuse and BD is significantly moderated by trauma exposure. This provides molecular insight into the complex mechanisms that link substance abuse, psychiatric disorders, and trauma exposure.

Original languageEnglish (US)
Pages (from-to)148-156
Number of pages9
JournalActa Psychiatrica Scandinavica
Issue number2
StatePublished - Feb 2018


  • alcohol
  • bipolar disorder
  • genetic epidemiology
  • trauma

ASJC Scopus subject areas

  • Psychiatry and Mental health


Dive into the research topics of 'Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers'. Together they form a unique fingerprint.

Cite this