Discovery Of The First Genome-Wide Significant Risk Loci For ADHD
By
Ditte Demontis,
Raymond K Walters,
Joanna Martin,
Manuel Mattheisen,
Thomas D Als,
Esben Agerbo,
Rich Belliveau,
Jonas Bybjerg-Grauholm,
Marie Baekvad-Hansen,
Felecia Cerrato,
Kimberly Chambert,
Claire Churchhouse,
Ashley Dumont,
Nicholas Eriksson,
Michael Gandal,
Jacqueline Goldstein,
Jakob Grove,
Christine S. Hansen,
Mads E Hauberg,
Mads V Hollegaard,
Daniel P Howrigan,
Hailiang Huang,
Julian Maller,
Alicia Martin,
Jennifer Moran,
Jonatan Pallesen,
Duncan S Palmer,
Carsten B Pedersen,
Marianne G Pedersen,
Timothy Poterba,
Jesper B Poulsen,
Stephan Ripke,
Elise B Robinson,
Kyle F Satterstrom,
Christine Stevens,
Patrick Turley,
Hyejung Won,
ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team,
Ole A Andreassen,
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 A. Rohde,
Panos Roussos,
Russell Schachar,
Pamela Sklar,
Edmund Sonuga-Barke,
Patrick F Sullivan,
Anita Thapar,
Joyce Tung,
Irwin Waldman,
Merete Nordentoft,
David M Hougaard,
Thomas Werge,
Ole Mors,
Preben Bo Mortensen,
M. Daly,
Stephen V Faraone,
Anders D Børglum,
Benjamin M Neale
Posted 03 Jun 2017
bioRxiv DOI: 10.1101/145581
(published DOI: 10.1038/s41588-018-0269-7)
Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of school-age children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no individual variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 ADHD 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 and loss-of-function intolerant genes, as well as around brain-expressed regulatory marks. These findings, based on clinical interviews and/or medical records are supported by additional analyses of a self-reported ADHD sample and a study of quantitative measures of ADHD symptoms in the population. Meta-analyzing these data with our primary scan yielded a total of 16 genome-wide significant loci. The results support the hypothesis that clinical diagnosis of ADHD is an extreme expression of one or more continuous heritable traits.
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