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

Demontis, Ditte, Walters, Raymond K., Martin, Joanna, Mattheisen, Manuel, Als, Thomas Damm, Agerbo, Esben, Baldursson, Gísli, Belliveau, Rich, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Cerrato, Felecia, Chambert, Kimberly, Churchhouse, Claire, Dumont, Ashley, Eriksson, Nicholas, Gandal, Michael, Goldstein, Jacqueline, Grasby, Katrina L., Grove, Jakob, Gudmundsson, Olafur O., Hansen, Christine S., Hauberg, Mads Engel, Hollegaard, Mads V., Howrigan, Daniel P., Huang, Hailiang, Maller, Julian, Martin, Alicia R., Martin, Nicholas G., Moran, Jennifer, Pallesen, Jonatan, Palmer, Duncan S., Bøcker Pedersen, Carsten, Giørtz Pedersen, Marianne, Poterba, Timothy, Buchhave Poulsen, Jesper, Ripke, Stephan, Robinson, Elise B., Satterstrom, F. Kyle, Stefansson, Hreinn, Stevens, Christine, Turley, Patrick, Walters, G. Bragi, Won, Hyejung, Wright, Margaret J., Andreassen, Ole A., Asherson, Philip, Burton, Christie, Boomsma, Dorret I., Cormand, Bru, Dalsgaard, Soren, Franke, Barbara, Gelernter, Joel, Geschwind, Daniel, Hakonarson, Hakon, Haavik, Jan, Kranzler, Henry, Kuntsi, Jonna, Langley, Kate, Lesch, Klaus-Peter, Middeldorp, Christel, Reif, Andreas, Rohde, Luis Augusto, Roussos, Panos, Schacha, Russell, Sklar, Pamela, Sonuga-Barke, Edmund J. S., Sullivan, Patrick F., Thapar, Anita, Tung, Joyce Y., Waldman, Irwin ., Medland, Sarah E., Stefansson, Kari, Nordentoft, Merete, Hougaard, David M., Werge, Thomas, Mors, Ole, Bo Mortensen, Preben, Daly, Mark J., Faraone, Stephen V., Børglum, Anders D., Neale, Benjamin M. and Anney, Richard 2019. Discovery of the first genome-wide significant risk loci for attention-deficit/hyperactivity disorder. Nature Genetics 51 , pp. 63-75. 10.1038/s41588-018-0269-7

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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 ADHD diagnosed cases and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, revealing new and important information on the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions, loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies; a cohort of diagnosed 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-spcific 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Psychology
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information: ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team,
Publisher: Nature
ISSN: 1061-4036
Date of First Compliant Deposit: 24 April 2018
Date of Acceptance: 28 September 2018
Last Modified: 15 Jun 2020 07:30
URI: http://orca-mwe.cf.ac.uk/id/eprint/110923

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