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Record W4296690675 · doi:10.1038/s41380-022-01776-4

Rare copy number variation in posttraumatic stress disorder

2022· article· en· W4296690675 on OpenAlexaff
Adam X. Maihofer, Worrawat Engchuan, Guillaume Huguet, Marieke Klein, Jeffrey R. MacDonald, Omar Shanta, Bhooma Thiruvahindrapuram, Martineau Jean‐Louis, Zohra Saci, Sébastien Jacquemont, Stephen W. Scherer, Elizabeth Ketema, Allison E. Aiello, Ananda B. Amstadter, Esmina Avdibegović, Dragan Babić, Dewleen G. Baker, Jonathan I. Bisson, Marco P. Boks, Elizabeth Bolger, Richard A. Bryant, Angela C. Bustamante, José Miguel Caldas‐de‐Almeida, Graça Cardoso, Jürgen Deckert, Douglas L. Delahanty, Katharina Domschke, Boadie W. Dunlop, Alma Džubur Kulenović, Alexandra Evans, Norah C. Feeny, Carol E. Franz, Aarti Gautam, Elbert Geuze, Afërdita Goçi, Rasha Hammamieh, Miro Jakovljević, Marti Jett, Ian Jones, Milissa L. Kaufman, Ronald C. Kessler, Anthony P. King, William S. Kremen, Bruce R. Lawford, Lauren A. M. Lebois, Israel Liberzon, Sarah D. Linnstaedt, Božo Lugonja, Jurjen J. Luykx, Michael J. Lyons, Matig Mavissakalian, Katie A. McLaughlin, Samuel A. McLean, Divya Mehta, Rebecca Mellor, C. Phillip Morris, Seid Muhie, Holly K. Orcutt, Matthew Peverill, Andrew Ratanatharathorn, Victoria B. Risbrough, Albert Rizzo, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy‐Byrne, Kenneth J. Ruggiero, Bart P. F. Rutten, Dick Schijven, Julia S. Seng, Christina M. Sheerin, Michael A. Sorenson, Martin H. Teicher, Monica Uddin, Robert J. Ursano, Christiaan H. Vinkers, Joanne Voisey, Heike Weber, Sherry Winternitz, Miguel Xavier, Ruoting Yang, Ross McD. Young, Lori A. Zoellner, Rany M. Salem, Richard A. Shaffer, Tianying Wu, Kerry J. Ressler, Murray B. Stein, Karestan C. Koenen, Jonathan Sebat, Caroline M. Nievergelt

Bibliographic record

VenueMolecular Psychiatry · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomic variations and chromosomal abnormalities
Canadian institutionsUniversity of TorontoUniversité de MontréalCentre Hospitalier Universitaire Sainte-JustineHospital for Sick Children
FundersU.S. Army Medical Research and Development CommandEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute on Drug AbuseNational Institute of Mental HealthMedical Research CouncilNational Institute on AgingU.S. Department of Health and Human ServicesNational Institutes of HealthU.S. Department of Veterans Affairs
KeywordsCopy-number variationGenome-wide association studyEtiologyPopulationPsychiatryGeneticsMedicinePsychologySingle-nucleotide polymorphismBiologyGeneGenomeGenotype

Abstract

fetched live from OpenAlex

Abstract Posttraumatic 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 (FDRq < 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.004
GPT teacher head0.217
Teacher spread0.213 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations6
Published2022
Admission routes1
Has abstractyes

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