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Record W3086124697 · doi:10.1101/2020.09.11.20175026

Genome-wide association meta-analysis of childhood and adolescent internalising symptoms

2020· preprint· en· W3086124697 on OpenAlexaff
Eshim S. Jami, Anke R. Hammerschlag, Hill F. Ip, Andrea G. Allegrini, Beben Benyamin, Richard Border, Elizabeth W. Diemer, Chang Jiang, Ville Karhunen, Yi Lu, Qing Lu, Travis T. Mallard, Pashupati P. Mishra, Ilja M. Nolte, Teemu Palviainen, Roseann E. Peterson, Hannah Sallis, Andrey A. Shabalin, Ashley Tate, Elisabeth Thiering, Natàlia Vilor‐Tejedor, Carol A. Wang, Ang Zhou, Daniel E. Adkins, Silvia Alemany, Helga Ask, Qi Chen, Robin P. Corley, Erik A. Ehli, Luke M. Evans, Alexandra Havdahl, Fiona A. Hagenbeek, Christian Hakulinen, Anjali K. Henders, Jouke‐Jan Hottenga, Tellervo Korhonen, Abdullah Al Mamun, Shelby Marrington, Alexander Neumann, Kaili Rimfeld, Fernando Rivadeneira, Judy L. Silberg, Catharina EM van Beijsterveldt, Eero Vuoksimaa, Alyce M. Whipp, Xiaoran Tong, Ole A. Andreassen, Dorret I. Boomsma, Sandra A. Brown, S. Alexandra Burt, William Copeland, E. Jane Costello, Danielle M. Dick, Lindon J. Eaves, K. Paige Harden, Kathleen Mullan Harris, Catharina A. Hartman, Joachim Heinrich, John K. Hewitt, Christian J. Hopfer, Elina Hyppönen, Marjo‐Riitta Järvelin, Jaakko Kaprio, Liisa Keltikangas‐Järvinen, Kelly L. Klump, Kenneth Krauter, Ralf Kuja‐Halkola, Henrik Larsson, Terho Lehtimäki, Paul Lichtenstein, Sebastian Lundström, Hermine H. Maes, Per Magnus, Marcus R. Munafò, Jake M. Najman, Pål R. Njølstad, Albertine J. Oldehinkel, Craig E. Pennell, Robert Plomin, Ted Reichborn‐Kjennerud, Chandra A. Reynolds, Richard J. Rose, Andrew Smolen, Harold Snieder, Michael C. Stallings, Marie Standl, Jordi Sunyer, Henning Tiemeier, Sally J. Wadsworth, Tamara L. Wall, Andrew Whitehouse, Gail Williams, Eivind Ystrøm, Michel G. Nivard, Meike Bartels, Christel M. Middeldorp

Bibliographic record

VenuemedRxiv · 2020
Typepreprint
Languageen
FieldPsychology
TopicChild and Adolescent Psychosocial and Emotional Development
Canadian institutionsJewish General Hospital
FundersMedical Research CouncilEuropean Commission
KeywordsAnxietyHeritabilityPsychologyGenome-wide association studyAttention deficit hyperactivity disorderAutism spectrum disorderLonelinessMeta-analysisAutismComorbidityClinical psychologyPsychiatryMedicineGeneticsSingle-nucleotide polymorphismBiologyInternal medicineGenotypeGene

Abstract

fetched live from OpenAlex

Abstract Internalising symptoms in childhood and adolescence are as heritable as adult depression and anxiety, yet little is known of their molecular basis. This genome-wide association meta-analysis of internalising symptoms included repeated observations from 64,641 individuals, aged between 3 and 18. The N-weighted meta-analysis of overall internalising symptoms (INT overall ) detected no genome-wide significant hits and showed low SNP heritability (1.66%, 95% confidence intervals 0.84-2.48%, N effective =132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalising symptoms showing the highest heritability (5.63%, 95% confidence intervals 3.08-8.18%). Additive genetic effects on internalising symptoms appeared stable over age, with overlapping estimates of SNP heritability from early-childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the wellbeing spectrum (| r g |> 0.70), as well as with insomnia, loneliness, attention-deficit hyperactivity disorder, autism, and childhood aggression (range | r g |=0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. The pattern of genetic correlations suggests that childhood and adolescent internalising symptoms share substantial genetic vulnerabilities with adult internalising disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalising symptoms over time and the high comorbidity amongst childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.171
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.049
GPT teacher head0.296
Teacher spread0.247 · 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 teacher head, not a consensus.

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

Citations10
Published2020
Admission routes1
Has abstractyes

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