Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains

Ditte Demontis, G Bragi Walters, Georgios Athanasiadis, Raymond Walters, Karen Therrien, Trine Tollerup Nielsen, Leila Farajzadeh, Georgios Voloudakis, Jaroslav Bendl, Biau Zeng, Wen Zhang, Jakob Grove, Thomas D Als, Jinjie Duan, F Kyle Satterstrom, Jonas Bybjerg-Grauholm, Marie Bækved-Hansen, Olafur O Gudmundsson, Sigurdur H Magnusson, Gisli BaldurssonKatrin Davidsdottir, Gyda S Haraldsdottir, Esben Agerbo, Gabriel E Hoffman, Søren Dalsgaard, Joanna Martin, Marta Ribasés, Dorret I Boomsma, Maria Soler Artigas, Nina Roth Mota, Daniel Howrigan, Sarah E Medland, Tetyana Zayats, Veera M Rajagopal, Merete Nordentoft, Ole Mors, David M Hougaard, Preben Bo Mortensen, Mark J Daly, Stephen V Faraone, Hreinn Stefansson, Panos Roussos, Barbara Franke, Thomas Werge, Benjamin M Neale, Kari Stefansson, Anders D Børglum*, ADHD Working Group of the Psychiatric Genomics Consortium

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.

Original languageEnglish
JournalNature Genetics
Pages (from-to)198-208
Number of pages11
Publication statusPublished - Feb 2023


  • Attention Deficit Disorder with Hyperactivity/genetics
  • Brain
  • Cognition
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans


Dive into the research topics of 'Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains'. Together they form a unique fingerprint.

Cite this