Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder
Выявление первых локусов риска синдрома дефицита внимания с гиперактивностью, достигших общегеномной значимости
2018-11-23
SCID: 54.1/9jb4pmm4
Discuss with AI
ADHDbrain-expressed regulatory markscommon genetic variantsgenome-wide association meta-analysisgenome-wide significant risk loci
Figures from the paper
Abstract (AI)
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.
Key Findings
1
A genome-wide association meta-analysis of 20,183 individuals with ADHD and 35,191 controls identified 12 independent genome-wide significant risk loci.
2
ADHD-associated variants were enriched in evolutionarily constrained genomic regions, loss-of-function-intolerant genes, and regulatory marks active in brain-expressed regions.
3
Genetic overlap with educational attainment differed across study designs, indicating study-specific patterns in ADHD-related genetic correlations.
4
Strong concordance between clinical ADHD GWAS and quantitative symptom GWAS supports ADHD diagnosis as an extreme expression of continuous heritable traits.
5
Three replication analyses supported the genetic associations, including studies of diagnosed ADHD, self-reported ADHD, and quantitative population symptom measures.
Research Object
ADHD susceptibility and its associated genetic loci in diagnosed individuals and population samples
Research Subject
genome-wide genetic associations and the biological and phenotypic characteristics of ADHD susceptibility, including its relationship to heritable symptom variation
Publication Details
Publication Date
2018-11-23
Journal
Publisher
ISSN
Open access PDF
Access Type
Author Information
Download PDF
Subscribe to digest