Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder
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.
|This work was funded by the European Commission 7th Framework Programme; grant id h2020/667302 - Comorbid Conditions of Attention deficit / hyperactivity disorder (CoCA), This work was funded by the European Commission 7th Framework Programme; grant id h2020/643051 - Mastering skills in the training Network for attention deficit hyperactivity and autism spectrum Disorders (MiND), This work was funded by the European Commission 7th Framework Programme; grant id fp7/602805 - Aggression subtyping for improved insight and treatment innovation in psychiatric disorders (AGGRESSOTYPE), This work was funded by the European Commission 7th Framework Programme; grant id fp7/602450 - IMAging GEnetics for MENtal Disorders (IMAGEMEND), This work was funded by the European Commission 7th Framework Programme; grant id fp7/278948 - Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes (TACTICS)|
Demontis, D, Walters, R.K, Martin, J. (Joanna), Mattheisen, M, Als, T.D. (Thomas D.), Agerbo, E, … Neale, B.M. (2018). Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics. doi:10.1038/s41588-018-0269-7