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

Nat Genet

Authors	Ditte Demontis Raymond Walters Joanna Martin Manuel Mattheisen Thomas Als Esben Agerbo Gísli Baldursson Rich Belliveau Jonas Bybjerg-Grauholm Marie Bækvad-Hansen Felecia Cerrato Kimberly Chambert Claire Churchhouse Ashley Dumont Nicholas Eriksson Michael Gandal Jacqueline Goldstein Katrina Grasby Jakob Grove Olafur Gudmundsson Christine Hansen Mads Hauberg Mads Hollegaard Daniel Howrigan Hailiang Huang Julian Maller Alicia Martin Nicholas Martin Jennifer Moran Jonatan Pallesen Duncan Palmer Carsten Pedersen Marianne Pedersen Timothy Poterba Jesper Poulsen Stephan Ripke Elise Robinson F Kyle Satterstrom Hreinn Stefansson Christine Stevens Patrick Turley G Bragi Walters Hyejung Won Margaret Wright ADHD Working Group of the Psychiatric Genomics Consortium (PGC) Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium 23andMe Research Team Ole Andreassen Philip Asherson Christie Burton Dorret Boomsma Bru Cormand Søren Dalsgaard Barbara Franke Joel Gelernter Daniel Geschwind Hakon Hakonarson Jan Haavik Henry Kranzler Jonna Kuntsi Kate Langley Klaus-Peter Lesch Christel Middeldorp Andreas Reif Luis Rohde Panos Roussos Russell Schachar Pamela Sklar Edmund Sonuga-Barke Patrick Sullivan Anita Thapar Joyce Tung Irwin Waldman Sarah Medland Kari Stefansson Merete Nordentoft David Hougaard Thomas Werge Ole Mors Preben Mortensen Mark Daly Stephen Faraone Anders Børglum Benjamin Neale
Keywords	Female Humans Male Gene Expression Regulation Genetic Predisposition to Disease Cohort Studies Adolescent Child Genome-Wide Association Study Polymorphism, Single Nucleotide Child, Preschool Genetic Loci Brain Risk Attention Deficit Disorder with Hyperactivity
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.
Year of Publication	2019
Journal	Nat Genet
Volume	51
Issue	1
Pages	63-75
Date Published	2019 01
ISSN	1546-1718
DOI	10.1038/s41588-018-0269-7
PubMed ID	30478444
Links	Google Scholar PubMed DOI
Grant list	R01 MH094469 / MH / NIMH NIH HHS / United States R00 MH113823 / MH / NIMH NIH HHS / United States G19/2 / Medical Research Council / United Kingdom U01 MH109536 / MH / NIMH NIH HHS / United States R01 MH107649 / MH / NIMH NIH HHS / United States U01 MH109539 / MH / NIMH NIH HHS / United States U01 MH094432 / MH / NIMH NIH HHS / United States MR/L010305/1 / Medical Research Council / United Kingdom