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

Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, Baldursson G, Belliveau R, Bybjerg-Grauholm J, Bækvad-Hansen M, Cerrato F, Chambert K, Churchhouse C, Dumont A, Eriksson N, Gandal M, Goldstein JI, Grasby KL, Grove J, Gudmundsson OO, Hansen CS, Hauberg ME, Hollegaard MV, Howrigan DP, Huang H, Maller JB, Martin AR, Martin NG, Moran J, Pallesen J, Palmer DS, Pedersen CB, Pedersen MG, Poterba T, Poulsen JB, Ripke S, Robinson EB, Satterstrom FK, Stefansson H, Stevens C, Turley P, Walters GB, Won H, Wright MJ, Albayrak Ö, Anney RJ, Arranz MJ, Banaschewski TJ, Bau C, Biederman J, Buitelaar JK, Casas M, Charach A, Crosbie J, Dempfle A, Doyle AE, Ebstein RP, Elia J, Freitag C, Föcker M, Gill M, Grevet E, Hawi Z, Hebebrand J, Herpertz-Dahlmann B, Hervas A, Hinney A, Hohmann S, Holmans P, Hutz M, Ickowitz A, Johansson S, Kent L, Kittel-Schneider S, Lambregts-Rommelse N, Lehmkuhl G, Loo SK, McGough JJ, Meyer J, Mick E, Middletion F, Miranda A, Mota NR, Mulas F, Mulligan A, Nelson F, Nguyen TT, Oades RD, O’Donovan MC, Owen MJ, Palmason H, Ramos-Quiroga JA, Renner TJ, Ribasés M, Rietschel M, Rivero O, Romanos J, Romanos M, Rothenberger A, Royers H, Sánchez-Mora C, Scherag A, Schimmelmann BG, Schäfer H, Sergeant J, Sinzig J, Smalley SL, Steinhausen HC, Thompson M, Todorov A, Vasquez AA, Walitza S, Wang Y, Warnke A, Williams N, Witt SH, Yang L, Zayats T, Zhang-James Y, Smith GD, Davies GE, Ehli EA, Evans DM, Fedko IO, Greven CU, Groen-Blokhuis MM, Guxens M, Hammerschlag AR, Hartman CA, Heinrich J, Jan Hottenga J, Hudziak J, Jugessur A, Kemp JP, Krapohl E, Murcia M, Myhre R, Nolte IM, Nyholt DR, Ormel J, Ouwens KG, Pappa I, Pennell CE, Plomin R, Ring S, Standl M, Stergiakouli E, Pourcain BS, Stoltenberg C, Sunyer J, Thiering E, Tiemeier H, Tiesler CM, Timpson NJ, Trzaskowski M, van der Most PJ, Vilor-Tejedor N, Wang CA, Whitehouse AJ, Zhao H, Agee M, Alipanahi B, Auton A, Bell RK, Bryc K, Elson SL, Fontanillas P, Furlotte NA, Hinds DA, Hromatka BS, Huber KE, Kleinman A, Litterman NK, McIntyre MH, Mountain JL, Northover CA, Pitts SJ, Sathirapongsasuti JF, Sazonova OV, Shelton JF, Shringarpure S, Tian C, Vacic V, Wilson CH, Andreassen OA, Asherson P, Burton CL, Boomsma DI, Cormand B, Dalsgaard S, Franke B, Gelernter J, Geschwind D, Hakonarson H, Haavik J, Kranzler HR, Kuntsi J, Langley K, Lesch KP, Middeldorp C, Reif A, Rohde LA, Roussos P, Schachar R, Sklar P, Sonuga-Barke EJ, Sullivan PF, Thapar A, Tung JY, Waldman ID, Medland SE, Stefansson K, Nordentoft M, Hougaard DM, Werge T, Mors O, Mortensen PB, Daly MJ, Faraone SV, Børglum AD, Neale BM (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 51

Pages Range: 63-75

Journal Issue: 1

DOI: 10.1038/s41588-018-0269-7

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.

Involved external institutions

Massachusetts General Hospital United States (USA) (US) Lundbeck Foundation Initiative for Integrative Psychiatric Research Denmark (DK) Landspítali / National University Hospital of Iceland Iceland (IS) University College Dublin (UCD) Ireland (IE) Philipps-Universität Marburg Germany (DE) Julius-Maximilians-Universität Würzburg Germany (DE) Universitätsklinikum Würzburg Germany (DE) Eli and Edythe L. Broad Institute of MIT and Harvard United States (USA) (US) State University of New York Upstate Medical University (SUNY) United States (USA) (US) University of València / Universitat de València Spain (ES) Universitätsklinikum Göttingen Germany (DE) Cardiff University United Kingdom (GB) Nemours/Alfred I. duPont Hospital for Children United States (USA) (US) The Jane and Terry Semel Institute for Neuroscience and Human Behavior United States (USA) (US) University of Zurich / Universität Zürich (UZH) Switzerland (CH) deCODE genetics Iceland (IS) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) MútuaTerrassa University Hospital / Hospital Universitario MútuaTerrassa / Hospital Universitari MútuaTerrassa Spain (ES) Ciber de Enfermedades Raras (CIBERER) Spain (ES) Autonomous University of Barcelona (UAB) / Universitat Autònoma de Barcelona Spain (ES) Icahn School of Medicine at Mount Sinai United States (USA) (US) King’s College London United Kingdom (GB) University of Bergen / Universitetet i Bergen Norway (NO) 23andMe United States (USA) (US) University of St Andrews United Kingdom (GB) Donders Institute for Brain, Cognition and Behaviour Netherlands (NL) Vrije Universiteit Amsterdam (VU) / University Amsterdam Netherlands (NL) University of California Los Angeles (UCLA) United States (USA) (US) Universität Trier Germany (DE) Universidade Federal do Rio Grande do Sul (UFRGS) Brazil (BR) University of Massachusetts Medical School United States (USA) (US) Hospital de Clínicas de Porto Alegre (HCPA) Brazil (BR) Universitätsklinikum Tübingen Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Universiteit Gent (UGent) / Ghent University Belgium (BE) Universität Duisburg-Essen (UDE) Germany (DE) Universität Bern Switzerland (CH) Universität zu Köln Germany (DE) Peking University Sixth Hospital China (CN) University of Bristol United Kingdom (GB) Avera Health United States (USA) (US) Radboud University Nijmegen Netherlands (NL) Instituto Valenciano de Neurología Pediátrica (INVANEP) Spain (ES) The Hospital for Sick Children (SickKids) Canada (CA) Karolinska Institute Sweden (SE) Emory University United States (USA) (US) Washington University in St. Louis United States (USA) (US) University of Southampton United Kingdom (GB) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen Netherlands (NL) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Norwegian Institute of Public Health (NIPH) / Folkehelseinstituttet Norway (NO) Aarhus University Denmark (DK) University of Queensland Australia (AU) Yale University United States (USA) (US) The Kids Research Institute Australia (prev. Telethon Kids Institute) Australia (AU) University of Pennsylvania (UPenn) United States (USA) (US) Instituto de Salud Global de Barcelona (ISGlobal) Spain (ES) Universitat de Barcelona (UB) / University of Barcelona Spain (ES) Queensland University of Technology (QUT) Australia (AU) Universitätsklinikum Essen Germany (DE) Christian-Albrechts-Universität zu Kiel Germany (DE) National University of Singapore (NUS) Singapore (SG) Universitat Pompeu Fabra (UPF) Spain (ES) St. James's Hospital Ireland (IE) Erasmus MC - Sophia Children’s Hospital Netherlands (NL) Monash University Australia (AU) Universitätsklinikum Aachen (UKA) Germany (DE) GGZ inGeest Netherlands (NL) University of Vermont United States (USA) (US)

How to cite

APA:

Demontis, D., Walters, R.K., Martin, J., Mattheisen, M., Als, T.D., Agerbo, E.,... Neale, B.M. (2019). Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics, 51(1), 63-75. https://doi.org/10.1038/s41588-018-0269-7

MLA:

Demontis, Ditte, et al. "Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder." Nature Genetics 51.1 (2019): 63-75.

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