Rare copy number variation in posttraumatic stress disorder
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Published:2022-09-21
Issue:12
Volume:27
Page:5062-5069
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ISSN:1359-4184
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Container-title:Molecular Psychiatry
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language:en
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Short-container-title:Mol Psychiatry
Author:
Maihofer Adam X., Engchuan Worrawat, Huguet GuillaumeORCID, Klein MariekeORCID, MacDonald Jeffrey R.ORCID, Shanta Omar, Thiruvahindrapuram BhoomaORCID, Jean-louis MartineauORCID, Saci Zohra, Jacquemont SebastienORCID, Scherer Stephen W., Ketema Elizabeth, Aiello Allison E., Amstadter Ananda B., Avdibegović Esmina, Babic Dragan, Baker Dewleen G.ORCID, Bisson Jonathan I., Boks Marco P.ORCID, Bolger Elizabeth A., Bryant Richard A.ORCID, Bustamante Angela C.ORCID, Caldas-de-Almeida Jose Miguel, Cardoso GraçaORCID, Deckert Jurgen, Delahanty Douglas L., Domschke KatharinaORCID, Dunlop Boadie W.ORCID, Dzubur-Kulenovic Alma, Evans Alexandra, Feeny Norah C., Franz Carol E., Gautam Aarti, Geuze ElbertORCID, Goci Aferdita, Hammamieh Rasha, Jakovljevic Miro, Jett MartiORCID, Jones IanORCID, Kaufman Milissa L., Kessler Ronald C.ORCID, King Anthony P., Kremen William S.ORCID, Lawford Bruce R., Lebois Lauren A. M.ORCID, Lewis Catrin, Liberzon Israel, Linnstaedt Sarah D.ORCID, Lugonja Bozo, Luykx Jurjen J.ORCID, Lyons Michael J., Mavissakalian Matig R., McLaughlin Katie A., McLean Samuel A., Mehta DivyaORCID, Mellor RebeccaORCID, Morris Charles PhillipORCID, Muhie Seid, Orcutt Holly K., Peverill Matthew, Ratanatharathorn Andrew, Risbrough Victoria B.ORCID, Rizzo AlbertORCID, Roberts Andrea L.ORCID, Rothbaum Alex O., Rothbaum Barbara O.ORCID, Roy-Byrne Peter, Ruggiero Kenneth J., Rutten Bart P. F.ORCID, Schijven Dick, Seng Julia S., Sheerin Christina M.ORCID, Sorenson Michael A., Teicher Martin H.ORCID, Uddin MonicaORCID, Ursano Robert J., Vinkers Christiaan H., Voisey JoanneORCID, Weber HeikeORCID, Winternitz SherryORCID, Xavier Miguel, Yang Ruoting, McD Young Ross, Zoellner Lori A., Salem Rany M.ORCID, Shaffer Richard A., Wu Tianying, Ressler Kerry J.ORCID, Stein Murray B.ORCID, Koenen Karestan C.ORCID, Sebat Jonathan, Nievergelt Caroline M., ,
Abstract
AbstractPosttraumatic stress disorder (PTSD) is a heritable (h2 = 24–71%) psychiatric illness. 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 = 0.029, SE = 0.005, P = 6.3 × 10−8). 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 = 0.0206, SE = 0.0056, P = 0.0002). 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 q < 0.05), 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.
Funder
U.S. Department of Health & Human Services | National Institutes of Health U.S. Department of Health & Human Services | NIH | National Institute of Mental Health
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Psychiatry and Mental health,Molecular Biology
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