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Record W3161677348 · doi:10.1101/2021.05.20.21257484

Identification of shared and differentiating genetic risk for autism spectrum disorder, attention deficit hyperactivity disorder and case subgroups

2021· preprint· en· W3161677348 on OpenAlexaff
Manuel Mattheisen, Jakob Grove, Thomas D. Als, Joanna Martin, Georgios Voloudakis, Sandra Meier, Ditte Demontis, Jaroslav Bendl, Raymond K. Walters, Caitlin E. Carey, Anders Rosengren, Nora I. Strom, Mads E. Hauberg, Biao Zeng, Gabriel E. Hoffman, Jonas Bybjerg‐Grauholm, Marie Bækvad‐Hansen, Esben Agerbo, Bru Cormand, Merete Nordentoft, Thomas Werge, Ole Mors, David M. Hougaard, Joseph D. Buxbaum, Stephen V. Faraone, Barbara Franke, Søren Dalsgaard, Preben Bo Mortensen, Elise Robinson, Panos Roussos, Benjamin M. Neale, Mark J. Daly, Anders D. Børglum

Bibliographic record

VenuemedRxiv · 2021
Typepreprint
Languageen
FieldNeuroscience
TopicAutism Spectrum Disorder Research
Canadian institutionsDalhousie University
FundersNational Institute of Mental HealthAgència de Gestió d'Ajuts Universitaris i de RecercaHorizon 2020 Framework ProgrammeNovo Nordisk FondenH. Lundbeck A/SLundbeckfondenMinisterio de Economía y CompetitividadNovo NordiskGeneralitat de CatalunyaAarhus UniversitetEuropean CommissionEuropean College of NeuropsychopharmacologyMinisterio de Ciencia, Innovación y UniversidadesNational Alliance for Research on Schizophrenia and Depression
KeywordsAttention deficit hyperactivity disorderAutism spectrum disorderGenetic architectureAutismNeuroticismComorbidityNeurodevelopmental disorderGenome-wide association studyPsychologyEtiologyClinical psychologyPsychiatryPhenotypeGeneticsSingle-nucleotide polymorphismGeneBiologyPersonalityGenotype

Abstract

fetched live from OpenAlex

Abstract Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental disorders with a considerable overlap in their genetic etiology. We dissected their shared and distinct genetic architecture by cross-disorder analyses of large data sets, including samples with information on comorbid diagnoses. We identified seven loci shared by the disorders and the first five genome-wide significant loci differentiating the disorders. All five differentiating loci showed opposite allelic directions in the two disorders separately as well as significant associations with variation in other traits e.g. educational attainment, items of neuroticism and regional brain volume. Integration with brain transcriptome data identified and prioritized several significantly associated genes. Genetic correlation of the shared liability across ASD-ADHD was strong for other psychiatric phenotypes while the ASD-ADHD differentiating liability correlated most strongly with cognitive traits. Polygenic score analyses revealed that individuals diagnosed with both ASD and ADHD are double-burdened with genetic risk for both disorders and show distinctive patterns of genetic association with other traits when compared to the ASD-only and ADHD-only subgroups. The results provide novel insights into the biological foundation for developing just one or both of the disorders and for driving the psychopathology discriminatively towards either ADHD or ASD.

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)0.003
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 score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0020.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0030.000

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 head0.028
GPT teacher head0.293
Teacher spread0.265 · 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

Citations1
Published2021
Admission routes1
Has abstractyes

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Same venuemedRxiv→Same topicAutism Spectrum Disorder Research→French-language works237,207→