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the association of genetic risks for mental disorders with alcohol misuse and nicotine dependence (<jats:styled-content style=\"fixed-case\">ND<\/jats:styled-content>) symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>High\u2010resolution polygenic risk scores (<jats:styled-content style=\"fixed-case\">PRS<\/jats:styled-content>s) were calculated for 10 732 <jats:styled-content style=\"fixed-case\">US<\/jats:styled-content> Army soldiers (8346 trauma\u2010exposed and 2386 trauma\u2010unexposed) based on genome\u2010wide association studies of bipolar disorder (<jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>), major depressive disorder, and schizophrenia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The main finding was a significant <jats:styled-content style=\"fixed-case\">BD PRS<\/jats:styled-content>\u2010by\u2010trauma interaction with respect to alcohol misuse (<jats:italic>P<\/jats:italic> = 6.07 \u00d7 10<jats:sup>\u22123<\/jats:sup>). We observed a positive correlation between <jats:styled-content style=\"fixed-case\">BD PRS<\/jats:styled-content> and alcohol misuse in trauma\u2010<jats:italic>exposed<\/jats:italic> soldiers (<jats:italic>r<\/jats:italic> = 0.029, <jats:italic>P<\/jats:italic> = 7.5 \u00d7 10<jats:sup>\u22123<\/jats:sup>) and a negative correlation in trauma\u2010<jats:italic>unexposed<\/jats:italic> soldiers (<jats:italic>r<\/jats:italic> = \u22120.071, <jats:italic>P<\/jats:italic> = 5.61 \u00d7 10<jats:sup>\u22124<\/jats:sup>). Consistent (nominally significant) result with concordant effect, directions were observed in the schizophrenia <jats:styled-content style=\"fixed-case\">PRS<\/jats:styled-content>\u2010by\u2010trauma interaction analysis. The variants included in the <jats:styled-content style=\"fixed-case\">BD PRS<\/jats:styled-content>\u2010by\u2010trauma interaction showed significant enrichments for gene ontologies related to high voltage\u2010gated calcium channel activity (<jats:styled-content style=\"fixed-case\">GO<\/jats:styled-content>:0008331, <jats:italic>P<\/jats:italic> = 1.51 \u00d7 10<jats:sup>\u22125<\/jats:sup>; <jats:styled-content style=\"fixed-case\">GO<\/jats:styled-content>:1990454, <jats:italic>P<\/jats:italic> = 4.49 \u00d7 10<jats:sup>\u22126<\/jats:sup>; <jats:styled-content style=\"fixed-case\">GO<\/jats:styled-content>:0030315, <jats:italic>P<\/jats:italic> = 2.07 \u00d7 10<jats:sup>\u22126<\/jats:sup>) and for Beta1\/Beta2 adrenergic receptor signaling pathways (<jats:italic>P<\/jats:italic> = 2.61 \u00d7 10<jats:sup>\u22124<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results indicate that the genetic overlap between alcohol misuse and <jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content> is significantly moderated by trauma exposure. This provides molecular insight into the complex mechanisms that link substance abuse, psychiatric disorders, and trauma exposure.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acps.12843","type":"journal-article","created":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T04:24:49Z","timestamp":1513052689000},"page":"148-156","source":"Crossref","is-referenced-by-count":18,"title":["Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of <scp>US<\/scp> soldiers"],"prefix":"10.1111","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0745-6046","authenticated-orcid":false,"given":"R.","family":"Polimanti","sequence":"first","affiliation":[{"name":"Department of Psychiatry Yale School of Medicine and VA CT Healthcare Center West Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Center for Child and Family Traumatic Stress Kennedy Krieger Institute Baltimore MD USA"},{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Yale University School of Public Health New Haven CT USA"},{"name":"Department of Genetics Yale University School of Medicine New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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