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Record W2802815532 · doi:10.1038/s41588-018-0269-7

Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder

2018· review· en· W2802815532 on OpenAlexafffund
Ditte Demontis, Raymond K. Walters, Joanna Martin, Manuel Mattheisen, Thomas D. Als, Esben Agerbo, Gísli Baldursson, Rich Belliveau, Jonas Bybjerg‐Grauholm, Marie Bækvad‐Hansen, Felecia Cerrato, Kimberly Chambert, Ashley Dumont, Nicholas Eriksson, Michael J. Gandal, Jacqueline I. Goldstein, Katrina L. Grasby, Jakob Grove, Ólafur Ó. Guðmundsson, Christine Søholm Hansen, Mads E. Hauberg, Mads V. Hollegaard, Daniel P. Howrigan, Hailiang Huang, Julian Maller, Alicia R. Martin, Nicholas G. Martin, Jennifer L. Moran, Jonatan Pallesen, Duncan S. Palmer, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Timothy Poterba, Jesper Buchhave Poulsen, Stephan Ripke, Elise Robinson, F. Kyle Satterstrom, Hreinn Stefánsson, Christine Stevens, Patrick Turley, G. Bragi Walters, Hyejung Won, Margaret J. Wright, Ole A. Andreassen, Philip Asherson, Christie L. Burton, Dorret I. Boomsma, Bru Cormand, Søren Dalsgaard, Barbara Franke, Joel Gelernter, Daniel H. Geschwind, Håkon Håkonarson, Jan Haavik, Henry R. Kranzler, Jonna Kuntsi, K. Langley, Klaus‐Peter Lesch, Christel M. Middeldorp, Andreas Reif, Luís Augusto Rohde, Panos Roussos, Russell Schachar, Pamela Sklar, Edmund Sonuga‐Barke, Patrick F. Sullivan, Anita Thapar, Joyce Y. Tung, Irwin D. Waldman, Sarah E. Medland, Kāri Stefánsson, Merete Nordentoft, David M. Hougaard, Thomas Werge, Ole Mors, Preben Bo Mortensen, Mark J. Daly, Stephen V. Faraone, Anders D. Børglum, Benjamin M. Neale

Bibliographic record

VenueNature Genetics · 2018
Typereview
Languageen
FieldMedicine
TopicAttention Deficit Hyperactivity Disorder
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
FundersCilagNational Institute of Diabetes and Digestive and Kidney DiseasesSeventh Framework ProgrammeAgència de Gestió d'Ajuts Universitaris i de RecercaNational Health and Medical Research CouncilMedical Research CouncilCanadian Institutes of Health ResearchNational Institutes of HealthServierNovo Nordisk FondenNorges ForskningsrådNational Institute of Mental HealthHorizon 2020 Framework ProgrammeAarhus UniversitetQIMR Berghofer Medical Research InstituteKU LeuvenEli Lilly and CompanyLundbeckfondenMinisterio de Economía y CompetitividadDeutsche ForschungsgemeinschaftKing's College LondonEuropean College of NeuropsychopharmacologyAlzheimer's AssociationAmerican Society of Clinical PsychopharmacologyNederlandse Organisatie voor Wetenschappelijk OnderzoekWellcome TrustH. Lundbeck A/SSunovionUniversitetet i BergenNovo NordiskGeneralitat de CatalunyaNational Institute for Health and Care ResearchMassachusetts General HospitalBroad InstituteIndiviorPfizerAction Medical ResearchU.S. Department of Veterans Affairs
KeywordsBiologyAttention deficit hyperactivity disorderGenome-wide association studyGenomeGeneticsComputational biologyGenePsychiatrySingle-nucleotide polymorphismGenotypePsychology

Abstract

fetched live from OpenAlex

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.

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)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Systematic review · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.002
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.030
GPT teacher head0.327
Teacher spread0.297 · 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 designSystematic review
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".

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Citations2,320
Published2018
Admission routes2
Has abstractyes

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