Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers. (11th December 2017)

• Record Type: Journal Article
• Authors: Polimanti, R.; Kaufman, J.; Zhao, H.; Kranzler, H. R.; Ursano, R. J.; Kessler, R. C.; Stein, M. B.; Gelernter, J.
• Other Names: Heeringa Steven investigator.; Wagner James investigator.; Cox Kenneth investigator.; Aliaga Pablo A. investigator.; Benedek COL David M. investigator.; Campbell‐Sills Laura investigator.; Fullerton Carol S. investigator.; Gebler Nancy investigator.; Gifford Robert K. investigator.; Hurwitz Paul E. investigator.; Jain Sonia investigator.; Lewandowski‐Romps Lisa investigator.; Herberman Mash Holly investigator.; McCarroll James E. investigator.; Naifeh James A. investigator.; Hinz Ng Tsz Hin investigator.; Nock Matthew K. investigator.; Santiago Patcho investigator.; Wynn Gary H. investigator.; Zaslavsky Alan M. investigator.
• Is Part Of: Acta psychiatrica Scandinavica. Volume 137:Number 2(2018)
• Page Start: 148
• Page End: 156
• Publication Date: 2017-12-11
• Subjects: alcohol -- bipolar disorder -- genetic epidemiology -- trauma; Psychiatry -- Periodicals; 616.89
• DOI: 10.1111/acps.12843
• Languages: English
• ISSNs: 0001-690X

Abstract

Abstract : 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.