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

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Main_text_ADHD_GWAS_submitted_revised_RW_DD_AB.pdf (1.020Mb)
Date
01/2019
Author
ADHD Working Group of the Psychiatric Genomics Consortium (PGC)
Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium
23andMe Research Team
Kent, Lindsey
Keywords
Adolescent
Attention Deficit Disorder with Hyperactivity/genetics
Brain/physiology
Child
Child, Preschool
Cohort Studies
Female
Gene Expression Regulation/genetics
Genetic Loci/genetics
Genetic Predisposition to Disease/genetics
Genome-Wide Association Study/methods
Humans
Male
Polymorphism, Single Nucleotide/genetics
Risk
QH426 Genetics
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
3rd-DAS
Metadata
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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 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.
Citation
ADHD Working Group of the Psychiatric Genomics Consortium (PGC) , Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium , 23andMe Research Team & Kent , L 2019 , ' Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder ' , Nature Genetics , vol. 51 , no. 1 , pp. 63-75 . https://doi.org/10.1038/s41588-018-0269-7
Publication
Nature Genetics
Status
Peer reviewed
DOI
https://doi.org/10.1038/s41588-018-0269-7
ISSN
1061-4036
Type
Journal article
Rights
Copyright © 2020 the Author(s). This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1038/s41588-018-0269-7.
Collections
  • University of St Andrews Research
URL
http://orca.cf.ac.uk/id/eprint/110923
URI
http://hdl.handle.net/10023/20827

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