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

Ditte Demontis, Raymond K. Walters, Joanna Martin, Manuel Mattheisen, Thomas D. Als, Esben Agerbo, G. sli Baldursson, Rich Belliveau, Jonas Bybjerg-Grauholm, Marie Bækvad-Hansen, Felecia Cerrato, Kimberly Chambert, Claire Churchhouse, Ashley Dumont, Nicholas Eriksson, Michael Gandal, Jacqueline I. Goldstein, Katrina L. Grasby, Jakob Grove, Olafur O. GudmundssonChristine S. Hansen, Mads Engel Hauberg, Mads V. Hollegaard, Daniel P. Howrigan, Hailiang Huang, Julian B. Maller, Alicia R. Martin, Nicholas G. Martin, Jennifer Moran, Jonatan Pallesen, Duncan S. Palmer, Carsten B. cker Pedersen, Marianne Giørtz Pedersen, Timothy Poterba, Jesper Buchhave Poulsen, Stephan Ripke, Elise B. Robinson, F. Kyle Satterstrom, Hreinn Stefansson, Christine Stevens, Patrick Turley, G. Bragi Walters, Hyejung Won, Margaret J. Wright, Özgür Albayrak, T. Trang Nguyen, David M. Evans, Maria M. Groen-Blokhuis, Anke R. Hammerschlag, Christel Middeldorp, ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Andreas Reif, Luis Augusto Rohde, Panos Roussos, Russell Schachar, Edmund J. S. Sonuga-Barke, Patrick Sullivan, Anita Thapar, Joyce Y. Tung, Irwin D. Waldman, Sarah E. Medland, Ole Mors, Preben Bo Mortensen, Mark J. Daly, Stephen V. Faraone, Anders D. Børglum, Benjamin M. Neale

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)63-75
Number of pages13
JournalNature Genetics
Volume51
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

Cite this

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