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Record W4411389345 · doi:10.1101/2025.06.15.25329656

Genome-wide meta-analysis identifies genetic risk factors and implicates multiple body systems in panic attacks and disorder

2025· preprint· en· W4411389345 on OpenAlexaff
Brittany L. Mitchell, Megan Skelton, Rujia Wang, Abigail ter Kuile, Alan E Murphy, Geneviève Morneau‐Vaillancourt, Danyang Li, Elham Assary, Matthew Hotopf, Jihua Hu, Chérie Armour, Andrew M. McIntosh, James Walters, Donald M. Lyall, Daniel J. Smıth, Nathalie Kingston, John R. Bradley, Gursharan Kalsi, Sang Hyuck Lee, Yuhao Lin, Evangelos Vassos, Saakshi Kakar, Laura Meldrum, Iona Smith, G. Ventura, Catherine M. Olsen, David C. Whiteman, Sarah E. Medland, Penelope A. Lind, Enda M. Byrne, Ian B. Hickie, Naomi R. Wray, Lukáš Mach, Michela Noseda, Andreas J. Forstner, Harold Snieder, Catharina A. Hartman, Nicholas G. Martin, Jürgen Deckert, Nathan Skene, Jonathan R. I. Coleman, Thalia C. Eley, Gerome Breen

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldEnvironmental Science
TopicHealth, Environment, Cognitive Aging
Canadian institutionsNutrasourceDouglas Mental Health University Institute
FundersNational Health and Medical Research CouncilMedical Research CouncilNIHR BioResourceKing's College LondonDepartment of Health and Social CareNational Institute for Health and Care ResearchQueensland HealthNHS Blood and Transplant
KeywordsPanic disorderMeta-analysisPanicGenome-wide association studyGenomeBiologyMedicineComputational biologyGeneticsPsychologyPsychiatryGeneAnxietyInternal medicineSingle-nucleotide polymorphismGenotype

Abstract

fetched live from OpenAlex

Abstract Panic attacks are sudden episodes of intense fear with physical and psychological symptoms, affecting approximately 28% of the population. Panic disorder (3-7% prevalence) involves recurrent attacks with persistent anticipatory worry, functional impairment, and avoidance. We conducted genome-wide association meta-analyses of a broad panic phenotype (panic attacks or panic disorder; 90,840 cases, 201,638 controls), panic disorder (41,721 cases, 201,638 controls), and isolated panic attacks (49,119 cases, 192,885 controls), identifying the first genome-wide significant variants for each trait (25 broad, 15 disorder, 5 attack). Gene-set analysis of single-cell RNA sequencing data for the broad phenotype implicated eye, heart, and lung neurons, pointing to sensory processing and interoceptive awareness. These peripheral neuronal associations generalised across psychiatric disorders. These findings offer novel insights into the biological mechanisms underlying panic and the overlooked role of afferent neurons across psychiatric disorders.

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)0.004
metaresearch head score (Gemma)0.012
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.014
Threshold uncertainty score0.046

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.012
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.010
Bibliometrics0.0020.003
Science and technology studies0.0000.000
Scholarly communication0.0020.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0140.001

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 head0.032
GPT teacher head0.277
Teacher spread0.245 · 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 designMeta-analysis
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

Citations1
Published2025
Admission routes1
Has abstractyes

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