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Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta\u2009=\u20090.029, SE\u2009=\u20090.005,<jats:italic>P<\/jats:italic>\u2009=\u20096.3\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta\u2009=\u20090.0206, SE\u2009=\u20090.0056,<jats:italic>P<\/jats:italic>\u2009=\u20090.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR<jats:italic>q<\/jats:italic>\u2009&lt;\u20090.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.<\/jats:p>","DOI":"10.1038\/s41380-022-01776-4","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T09:18:35Z","timestamp":1663751915000},"page":"5062-5069","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Rare copy number variation in posttraumatic stress disorder"],"prefix":"10.1038","volume":"27","author":[{"given":"Adam 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