Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder
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Abstract
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.
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The record
- Venue
- Nature Genetics
- Topic
- Attention Deficit Hyperactivity Disorder
- Field
- Medicine
- Canadian institutions
- SickKids FoundationHospital for Sick ChildrenUniversity of Toronto
- Funders
- CilagNational 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
- Keywords
- BiologyAttention deficit hyperactivity disorderGenome-wide association studyGenomeGeneticsComputational biologyGenePsychiatrySingle-nucleotide polymorphismGenotypePsychology
- Has abstract in OpenAlex
- yes