| Literature DB >> 30478444 |
Ditte Demontis1,2,3, Raymond K Walters4,5, Joanna Martin5,6,7, Manuel Mattheisen1,2,3,8,9,10, Thomas D Als1,2,3, Esben Agerbo1,11,12, Gísli Baldursson13, Rich Belliveau5, Jonas Bybjerg-Grauholm1,14, Marie Bækvad-Hansen1,14, Felecia Cerrato5, Kimberly Chambert5, Claire Churchhouse4,5,15, Ashley Dumont5, Nicholas Eriksson16, Michael Gandal17,18,19,20, Jacqueline I Goldstein4,5,15, Katrina L Grasby21, Jakob Grove1,2,3,22, Olafur O Gudmundsson13,23,24, Christine S Hansen1,14,25, Mads Engel Hauberg1,2,3, Mads V Hollegaard1,14, Daniel P Howrigan4,5, Hailiang Huang4,5, Julian B Maller5,26, Alicia R Martin4,5,15, Nicholas G Martin21, Jennifer Moran5, Jonatan Pallesen1,2,3, Duncan S Palmer4,5, Carsten Bøcker Pedersen1,11,12, Marianne Giørtz Pedersen1,11,12, Timothy Poterba4,5,15, Jesper Buchhave Poulsen1,14, Stephan Ripke4,5,27, Elise B Robinson4,28, F Kyle Satterstrom4,5,15, Hreinn Stefansson23, Christine Stevens5, Patrick Turley4,5, G Bragi Walters23,24, Hyejung Won17,18, Margaret J Wright29, Ole A Andreassen30, Philip Asherson31, Christie L Burton32, Dorret I Boomsma33,34, Bru Cormand35,36,37,38, Søren Dalsgaard11, Barbara Franke39, Joel Gelernter40,41, Daniel Geschwind17,18,19, Hakon Hakonarson42, Jan Haavik43,44, Henry R Kranzler45,46, Jonna Kuntsi31, Kate Langley7,47, Klaus-Peter Lesch48,49,50, Christel Middeldorp33,51,52, Andreas Reif53, Luis Augusto Rohde54,55, Panos Roussos56,57,58,59, Russell Schachar32, Pamela Sklar56,57,58, Edmund J S Sonuga-Barke60, Patrick F Sullivan6,61, Anita Thapar7, Joyce Y Tung16, Irwin D Waldman62, Sarah E Medland21, Kari Stefansson23,24, Merete Nordentoft1,63, David M Hougaard1,14, Thomas Werge1,25,64, Ole Mors1,65, Preben Bo Mortensen1,2,11,12, Mark J Daly4,5,15,66, Stephen V Faraone67, Anders D Børglum68,69,70, Benjamin M Neale71,72,73.
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.Entities:
Mesh：
Year: 2018 PMID： 30478444 PMCID： PMC6481311 DOI： 10.1038/s41588-018-0269-7
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330