{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T17:55:27Z","timestamp":1793555727880,"version":"4.5.0"},"reference-count":54,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2022,11,1]]},"abstract":"<jats:sec id=\"ab-yoi220062-4\"><jats:title>Importance<\/jats:title><jats:p>Self-reported trauma exposure has consistently been found to be a risk factor for major depressive disorder (MDD), and several studies have reported interactions with genetic liability. To date, most studies have examined gene-environment interactions with trauma exposure using genome-wide variants (single-nucleotide variations [SNVs]) or polygenic scores, both typically capturing less than 3% of phenotypic risk variance.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi220062-5\"><jats:title>Objective<\/jats:title><jats:p>To reexamine genome-by-trauma interaction associations using genetic measures using all available genotyped data and thus, maximizing accounted variance.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi220062-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>The UK Biobank study was conducted from April 2007 to May 1, 2016 (follow-up mental health questionnaire). The current study used available cross-sectional genomic and trauma exposure data from UK Biobank. Participants who completed the mental health questionnaire and had available genetic, trauma experience, depressive symptoms, and\/or neuroticism information were included. Data were analyzed from April 1 to August 30, 2021.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi220062-7\"><jats:title>Exposures<\/jats:title><jats:p>Trauma and genome-by-trauma exposure interactions.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi220062-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Measures of self-reported depression, neuroticism, and trauma exposure with whole-genome SNV data are available from the UK Biobank study. Here, a mixed-model statistical approach using genetic, trauma exposure, and genome-by-trauma exposure interaction similarity matrices was used to explore sources of variation in depression and neuroticism.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi220062-9\"><jats:title>Results<\/jats:title><jats:p>Analyses were conducted on 148\u202f129 participants (mean [SD] age, 56 [7] years) of which 76\u202f995 were female (52.0%). The study approach estimated the heritability (SE) of MDD to be approximately 0.160 (0.016). Subtypes of self-reported trauma exposure (catastrophic, adult, childhood, and full trauma) accounted for a significant proportion of the variance of MDD, with heritability (SE) ranging from 0.056 (0.013) to 0.176 (0.025). The proportion of MDD risk variance accounted for by significant genome-by-trauma interaction revealed estimates (SD) ranging from 0.074 (0.006) to 0.201 (0.009). Results from sex-specific analyses found genome-by-trauma interaction variance estimates approximately 5-fold greater for MDD in male participants (0.441 [0.018]) than in female participants (0.086 [0.009]).<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi220062-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>This cross-sectional study used an approach combining all genome-wide SNV data when exploring genome-by-trauma interactions in individuals with MDD; findings suggest that such interactions were associated with depression manifestation. Genome-by-trauma interaction accounts for greater trait variance in male individuals, which points to potential differences in depression etiology between the sexes. The methodology used in this study can be extrapolated to other environmental factors to identify modifiable risk environments and at-risk groups to target with interventions.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2022.2983","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T15:32:34Z","timestamp":1664379154000},"page":"1110","source":"Crossref","is-referenced-by-count":27,"title":["Genome-by-Trauma Exposure Interactions in Adults With Depression in the UK Biobank"],"prefix":"10.1001","volume":"79","author":[{"given":"Melisa","family":"Chuong","sequence":"first","affiliation":[{"name":"Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, United Kingdom"},{"name":"Department of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex S. 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