Discovery Of The First Genome-Wide Significant Risk Loci For ADHD
Raymond K Walters,
Thomas D. Als,
Christine S. Hansen,
Mads E Hauberg,
Mads V Hollegaard,
Daniel P Howrigan,
Alicia R. Martin,
Duncan S. Palmer,
Carsten B Pedersen,
Marianne G Pedersen,
Jesper B Poulsen,
Elise B Robinson,
Kyle F Satterstrom,
ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team,
Ole A. Andreassen,
Luis A. Rohde,
Patrick F Sullivan,
David M Hougaard,
Preben B Mortensen,
Mark J. 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)
Posted 03 Jun 2017
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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