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Record W4297242151 · doi:10.1038/s41588-022-01171-3

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

2022· article· en· W4297242151 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, Wen Zhang, 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

VenueNature Genetics · 2022
Typearticle
Languageen
FieldNeuroscience
TopicAutism Spectrum Disorder Research
Canadian institutionsDalhousie University
FundersNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Mental HealthNational Institute on AgingAgència de Gestió d'Ajuts Universitaris i de RecercaNational Institutes of HealthH. Lundbeck A/SHorizon 2020 Framework ProgrammeNovo Nordisk FondenLundbeckfondenMinisterio de Economía y CompetitividadNovo NordiskGeneralitat de CatalunyaAarhus UniversitetEuropean CommissionWellcome TrustEuropean College of NeuropsychopharmacologyMinisterio de Ciencia, Innovación y UniversidadesNational Alliance for Research on Schizophrenia and Depression
KeywordsAutism spectrum disorderBiologyAttention deficit hyperactivity disorderGenetic architectureIdentification (biology)GeneticsAutismNeurodevelopmental disorderDevelopmental psychologyClinical psychologyPsychologyGenePhenotypeEcology

Abstract

fetched live from OpenAlex

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits, including educational attainment, neuroticism and regional brain volume. Integration with brain transcriptome data enabled us to identify and prioritize several significantly associated genes. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups. These results provide insights into the biological foundation of the development of one or both conditions and of the factors driving psychopathology discriminatively toward 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)0.002
metaresearch head score (Gemma)0.004
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 score0.004
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.004
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.002
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0010.002
Research integrity0.0010.001
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 head0.014
GPT teacher head0.279
Teacher spread0.266 · 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

Citations76
Published2022
Admission routes1
Has abstractyes

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