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Record W4318071643 · doi:10.1038/s41588-022-01285-8

Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains

2023· review· en· W4318071643 on OpenAlexaff
Ditte Demontis, G. Bragi Walters, Georgios Athanasiadis, Raymond K. Walters, Karen Therrien, Trine Tollerup Nielsen, Leila Farajzadeh, Georgios Voloudakis, Jaroslav Bendl, Biau Zeng, Wen Zhang, Jakob Grove, Thomas D. Als, Jinjie Duan, F. Kyle Satterstrom, Jonas Bybjerg‐Grauholm, Marie Bækved-Hansen, Ólafur Ó. Guðmundsson, Sigurður H. Magnússon, Gísli Baldursson, Katrín Davíðsdóttir, Gyða S. Haraldsdóttir, Esben Agerbo, Gabriel E. Hoffman, Søren Dalsgaard, Joanna Martin, Marta Ribasés, Dorret I. Boomsma, María Soler Artigas, Nina Roth Mota, Daniel P. Howrigan, Sarah E. Medland, Tetyana Zayats, Veera M. Rajagopal, Alexandra Havdahl, Alysa E. Doyle, Andreas Reif, Anita Thapar, Bru Cormand, Calwing Liao, Christie L. Burton, Claiton H.D. Bau, Diego Luiz Rovaris, Edmund Sonuga‐Barke, Elizabeth C. Corfield, Eugênio H. Grevet, Henrik Larsson, Ian R. Gizer, Irwin D. Waldman, Isabell Brikell, Jan Haavik, Jennifer Crosbie, James J. McGough, Jonna Kuntsi, Joseph Glessner, K. Langley, Klaus‐Peter Lesch, Luís Augusto Rohde, Mara Helena Hutz, Marieke Klein, Mark A. Bellgrove, Martin Tesli, Michael O‘Donovan, Ole A. Andreassen, Patrick W. L. Leung, Pedro Mário Pan, Ridha Joober, Russell Schachar, Sandra K. Loo, Stephanie H. Witt, Ted Reichborn‐Kjennerud, Tobias Banaschewski, Ziarih Hawi, Mark J. Daly, Ole Mors, Merete Nordentoft, David M. Hougaard, Preben Bo Mortensen, Stephen V. Faraone, Hreinn Stefánsson, Panos Roussos, Barbara Franke, Thomas Werge, Benjamin M. Neale, Kāri Stefánsson, Anders D. Børglum

Bibliographic record

VenueNature Genetics · 2023
Typereview
Languageen
FieldMedicine
TopicAttention Deficit Hyperactivity Disorder
Canadian institutionsHospital for Sick ChildrenDouglas Mental Health University InstituteMcGill University
FundersNational Institute of Mental HealthInstituto de Salud Carlos IIIAgència de Gestió d'Ajuts Universitaris i de RecercaMedical Research CouncilNational Institutes of HealthNational Health and Medical Research CouncilHorizon 2020 Framework ProgrammeNorges ForskningsrådNovo Nordisk FondenNederlandse Organisatie voor Wetenschappelijk OnderzoekH. Lundbeck A/SLundbeckfondenNovo NordiskGeneralitat de CatalunyaEuropean Regional Development FundAarhus UniversitetEuropean CommissionEuropean College of NeuropsychopharmacologyMinisterio de Ciencia, Innovación y Universidades
KeywordsBiologyGenetic architectureGenome-wide association studyComputational biologyCognitionGeneticsGenomeEvolutionary biologyQuantitative trait locusNeuroscienceSingle-nucleotide polymorphismGeneGenotype

Abstract

fetched live from OpenAlex

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.003
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0030.003
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.092
GPT teacher head0.429
Teacher spread0.337 · 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 designNot applicable
Domainnot available
GenreReview

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

Citations760
Published2023
Admission routes1
Has abstractyes

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