@article{d40603db383b4933b107f5b2d73c10a7,
title = "Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers",
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.",
keywords = "alcohol, bipolar disorder, genetic epidemiology, trauma",
author = "R. Polimanti and J. Kaufman and H. Zhao and Kranzler, {H. R.} and Ursano, {R. J.} and Kessler, {R. C.} and Stein, {M. B.} and J. Gelernter",
note = "Funding Information: This study was funded by National Institutes of Health grants R21 AA024404, RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535, P50 AA012870, U01 MH109532, and the VISN1 and VISN4 MIR-ECCs. Army STARRS was sponsored by the Department of the Army and funded under cooperative agreement number U01 MH087981 (2009-2015) with the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIH/NIMH). Subsequently, STARRS-LS was sponsored and funded by the Department of Defense (USUHS grant number HU0001-15-2-0004). The contents are solely the responsibility of the authors and do not necessarily represent the views of the Department of Health and Human Services, NIMH, or the Department of the Army, or the Department of Defense. Funding Information: Dr. Stein has in the last three years been a consultant for Acte-lion Pharmaceuticals, Healthcare Management Technologies, Janssen, Neurocrine, Pfizer, Resilience Therapeutics, Tonix Pharmaceuticals, and Oxeia Biopharmaceuticals. Dr. Kaufman has provided consultation to Pfizer and Merck Pharmaceutical Company to train investigators to assess bipolar disorder in youth. Dr. Kranzler has been an advisory board member, consultant, or CME speaker for Indivior, Lundbeck, and Otsuka. He is also a member of the American Society of Clinical Psychopharmacology{\textquoteright}s Alcohol Clinical Trials Initiative, which is supported by AbbVie, Alkermes, Ethypharm, Indivior, Lilly, Lundbeck, Pfizer, and XenoPort. In the past 3 years, Dr. Kessler received support for his epidemiological studies from Sanofi Aventis; was a consultant for Johnson & Johnson Wellness and Prevention, Shire, Takeda; and served on an advisory board for the Johnson & Johnson Services Inc. Lake Nona Life Project. Kessler is a co-owner of DataStat, Inc., a market research firm that carries out healthcare research. The other authors reported no biomedical financial interests or potential conflict of interests. Funding Information: This study was funded by National Institutes of Health grants R21 AA024404, RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535, P50 AA012870, U01 MH109532, and the VISN1 and VISN4 MIRECCs. Army STARRS was sponsored by the Department of the Army and funded under cooperative agreement number U01 MH087981 (2009-2015) with the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIH/NIMH). Subsequently, STARRS-LS was sponsored and funded by the Department of Defense (USUHS grant number HU0001-15-2-0004). The contents are solely the responsibility of the authors and do not necessarily represent the views of the Department of Health and Human Services, NIMH, or the Department of the Army, or the Department of Defense. The Army STARRS Team consists of Co-Principal Investigators: Robert J. Ursano, MD (Uniformed Services University of the Health Sciences) and Murray B. Stein, MD, MPH (University of California San Diego and VA San Diego Healthcare System). Site Principal Investigators: Steven Heeringa, PhD (University of Michigan), James Wagner, PhD (University of Michigan), and Ronald C. Kessler, PhD (Harvard Medical School). Army liaison/consultant: Kenneth Cox, MD, MPH (US Army Public Health Center). Other team members: Pablo A. Aliaga, MA (Uniformed Services University of the Health Sciences); COL David M. Benedek, MD (Uniformed Services University of the Health Sciences); Laura Campbell-Sills, PhD (University of California San Diego); Carol S. Fullerton, PhD (Uniformed Services University of the Health Sciences); Nancy Gebler, MA (University of Michigan); Robert K. Gifford, PhD (Uniformed Services University of the Health Sciences); Paul E. Hurwitz, MPH (Uniformed Services University of the Health Sciences); Sonia Jain, PhD (University of California San Diego); Tzu-Cheg Kao, PhD (Uniformed Services University of the Health Sciences); Lisa Lewandowski-Romps, PhD (University of Michigan); Holly Herberman Mash, PhD (Uniformed Services University of the Health Sciences); James E. McCarroll, PhD, MPH (Uniformed Services University of the Health Sciences); James A. Naifeh, PhD (Uniformed Services University of the Health Sciences); Tsz Hin Hinz Ng, MPH (Uniformed Services University of the Health Sciences); Matthew K. Nock, PhD (Harvard University); Nancy A. Sampson, BA (Harvard Medical School); CDR Patcho Santiago, MD, MPH (Uniformed Services University of the Health Sciences); LTC Gary H. Wynn, MD (Uniformed Services University of the Health Sciences); and Alan M. Zaslavsky, PhD (Harvard Medical School). Publisher Copyright: {\textcopyright} 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",
year = "2018",
month = feb,
doi = "10.1111/acps.12843",
language = "English (US)",
volume = "137",
pages = "148--156",
journal = "Acta Psychiatrica Scandinavica",
issn = "0001-690X",
publisher = "Wiley-Blackwell",
number = "2",
}