Discovery Of The First Genome-Wide Significant Risk Loci For ADHD

Demontis, D.; Walters, R. K.; Martin, J.; Mattheisen, M.; Als, T. D.; Agerbo, E.; Belliveau, R.; Bybjerg-Grauholm, J.; Baekved-Hansen, M.; Cerrato, F.; Chambert, K.; Churchhouse, C.; Dumont, A.; Eriksson, N.; Gandal, M.; Goldstein, J.; Grove, J.; Hansen, C. S.; Hauberg, M.; Hollegaard, M.; Howrigan, D. P.; Huang, H.; Maller, J.; Martin, A. R.; Moran, J.; Pallesen, J.; Palmer, D. S.; Pedersen, C. B.; Pedersen, M. G.; Poterba, T.; Poulsen, J. B.; Ripke, S.; Robinson, E. B.; Satterstrom, F. K.; Stevens, C.; Turley, P.; Won, H.; - ADHD Working Group of the Psychiatric Genomics Con,; - Early Life

doi:10.1101/145581

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bioRxiv · 10.1101/145581

Discovery Of The First Genome-Wide Significant Risk Loci For ADHD

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Abstract

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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Demontis, D., Walters, R. K., Martin, J., Mattheisen, M., Als, T. D., Agerbo, E., Belliveau, R., Bybjerg-Grauholm, J., Baekved-Hansen, M., Cerrato, F., Chambert, K., Churchhouse, C., Dumont, A., Eriksson, N., Gandal, M., Goldstein, J., Grove, J., Hansen, C. S., Hauberg, M., Hollegaard, M., Howrigan, D. P., Huang, H., Maller, J., Martin, A. R., Moran, J., Pallesen, J., Palmer, D. S., Pedersen, C. B., Pedersen, M. G., Poterba, T., Poulsen, J. B., Ripke, S., Robinson, E. B., Satterstrom, F. K., Stevens, C., Turley, P., Won, H., - ADHD Working Group of the Psychiatric Genomics Con,, - Early Life. 2017-06-03. Discovery Of The First Genome-Wide Significant Risk Loci For ADHD. https://doi.org/10.1101/145581

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