{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:06:16Z","timestamp":1791576376166,"version":"4.3.4"},"reference-count":11,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:sec id=\"ab-ybr250002-4\"><jats:title>Importance<\/jats:title><jats:p>Traumatic brain injury is common and occurs across all ages. Observational studies have shown that traumatic brain injury is associated with a wide range of mental disorders and suicide. Whether these associations represent a causal effect is, however, difficult to establish, and confounding by genetic liability for mental disorder may play a substantial role.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ybr250002-5\"><jats:title>Objective<\/jats:title><jats:p>To investigate whether observational associations between traumatic brain injury and mental disorder or suicide could be confounded by genetic liability for mental disorder.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ybr250002-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This cohort study was conducted from October 2023 to January 2025. The study population consisted of the general population subcohort of the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) sample, which is a representative sample of the Danish population born between 1981 and 2008 that has been genotyped.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ybr250002-7\"><jats:title>Exposures<\/jats:title><jats:p>Polygenic risk scores (PRSs) for schizophrenia, bipolar disorder, depression, and attention-deficit\/hyperactivity disorder (ADHD) calculated from the genotypes and genome-wide association summary statistics.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ybr250002-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary outcome was traumatic brain injury, operationalized via hospital diagnoses. The associations between PRSs for schizophrenia, bipolar disorder, depression, and ADHD, respectively, and traumatic brain injury were examined via Cox proportional hazards regression, yielding hazard rate ratios (HRRs) with 95% confidence intervals.<\/jats:p><\/jats:sec><jats:sec id=\"ab-ybr250002-9\"><jats:title>Results<\/jats:title><jats:p>The final cohort consisted of a total of 40\u202f274 individuals, of whom 19\u202f802 (49.2%) were female. A total of 3341 (8.3%) of the cohort members (of whom 1464 [43.8%] were female and 1877 [56.2%] were male) experienced traumatic brain injury during follow-up. All 4 PRSs showed statistically significant positive associations with traumatic brain injury (PRS-schizophrenia: HRR, 1.06; 95% CI, 1.02-1.10; <jats:italic>P<\/jats:italic>\u2009=\u2009.002; PRS-bipolar disorder: HRR, 1.04; 95% CI, 1.00-1.08; <jats:italic>P<\/jats:italic>\u2009=\u2009.04; PRS-depression: HRR, 1.10; 95% CI, 1.06-1.14; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001; and PRS-ADHD: HRR, 1.12; 95% CI, 1.08-1.16; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001).<\/jats:p><\/jats:sec><jats:sec id=\"ab-ybr250002-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>The results of this cohort study suggest that confounding by genetic liability for mental disorder could explain some of the association between traumatic brain injury and mental disorder or suicide. Consequently, genetic liability for mental disorder should be factored into future studies of these associations to avoid overestimation of causality.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2025.0318","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T15:31:19Z","timestamp":1743607879000},"page":"622","source":"Crossref","is-referenced-by-count":5,"title":["Genetic Confounding in the Association Between Traumatic Brain Injury and Mental Disorder or Suicide"],"prefix":"10.1001","volume":"82","author":[{"given":"S\u00f8ren Dinesen","family":"\u00d8stergaard","sequence":"first","affiliation":[{"name":"Department of Affective Disorders, Aarhus University Hospital \u2013 Psychiatry, Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Mundy","sequence":"additional","affiliation":[{"name":"Department of Affective Disorders, Aarhus University Hospital \u2013 Psychiatry, Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha Silvia Mercedes","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Affective Disorders, Aarhus University Hospital \u2013 Psychiatry, Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Musliner","sequence":"additional","affiliation":[{"name":"Department of Affective Disorders, Aarhus University Hospital \u2013 Psychiatry, Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"4","key":"ybr250002r1","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.3171\/2017.10.JNS17352","article-title":"Estimating the global incidence of traumatic brain injury.","volume":"130","author":"Dewan","year":"2018","journal-title":"J Neurosurg"},{"issue":"1","key":"ybr250002r2","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/S1474-4422(18)30415-0","article-title":"Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.","volume":"18","author":"GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators","year":"2019","journal-title":"Lancet Neurol"},{"key":"ybr250002r3","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2024.115990","article-title":"Impact of traumatic brain injury on risk for schizophrenia and bipolar 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J, Pedersen? CB, B\u00e6kvad-Hansen? M, . The iPSYCH2015 Case-Cohort sample: updated directions for unravelling genetic and environmental architectures of severe mental disorders.? medRxiv. 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