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

23andMe Research Team, ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium

Research output: Contribution to journalArticle

78 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)63-75
Number of pages13
JournalNature Genetics
Volume51
Issue number1
Early online date26 Nov 2018
DOIs
Publication statusPublished - 1 Jan 2019

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Attention Deficit Disorder with Hyperactivity
Genome
Genome-Wide Association Study
Meta-Analysis
Population
Cohort Studies
Brain

Cite this

23andMe Research Team, ADHD Working Group of the Psychiatric Genomics Consortium (PGC), & Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium (2019). Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics, 51(1), 63-75. https://doi.org/10.1038/s41588-018-0269-7
23andMe Research Team ; ADHD Working Group of the Psychiatric Genomics Consortium (PGC) ; Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium. / Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. In: Nature Genetics. 2019 ; Vol. 51, No. 1. pp. 63-75.
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23andMe Research Team, ADHD Working Group of the Psychiatric Genomics Consortium (PGC) & Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium 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

Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. / 23andMe Research Team; ADHD Working Group of the Psychiatric Genomics Consortium (PGC); Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium.

In: Nature Genetics, Vol. 51, No. 1, 01.01.2019, p. 63-75.

Research output: Contribution to journalArticle

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AU - Hollegaard, Mads V.

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AU - Moran, Jennifer

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AU - Palmer, Duncan S.

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N2 - 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.

AB - 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.

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23andMe Research Team, ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics. 2019 Jan 1;51(1):63-75. https://doi.org/10.1038/s41588-018-0269-7