The molecular genetic architecture of attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition which affects 2–10% of school age children worldwide. Although the underlying molecular mechanism for the disorder is poorly understood, familial, twin and adoption studies suggest a strong genetic component....

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Vydáno v:	Molecular psychiatry Ročník 20; číslo 3; s. 289 - 297
Hlavní autoři:	Hawi, Z, Cummins, T D R, Tong, J, Johnson, B, Lau, R, Samarrai, W, Bellgrove, M A
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 01.03.2015 Nature Publishing Group
Témata:	692/699/476/1311 Alzheimer's disease Attention Deficit Disorder with Hyperactivity - genetics Attention deficit hyperactivity disorder Behavioral Sciences Biological Psychology Care and treatment Cell adhesion & migration Children Copy number Disease DNA Copy Number Variations - genetics Dopamine Dopamine D4 receptors Dopamine D5 receptors Dopamine receptors expert-review Fructose Genes Genetic aspects Genetic diversity Genetic Predisposition to Disease - genetics Genetics Genome-Wide Association Study Genomes Glutamate receptors Health risk assessment Humans Hyperactivity Hypotheses Kinases Medicine Medicine & Public Health Neurosciences Nitric-oxide synthase Oxidoreductase Pharmacotherapy Physiological aspects Psychiatry Risk factors Signal transduction Single nucleotide polymorphisms Single-nucleotide polymorphism SNAP-25 protein Twins United States Australia
ISSN:	1359-4184, 1476-5578, 1476-5578
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Shrnutí:	Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition which affects 2–10% of school age children worldwide. Although the underlying molecular mechanism for the disorder is poorly understood, familial, twin and adoption studies suggest a strong genetic component. Here we provide a state-of-the-art review of the molecular genetics of ADHD incorporating evidence from candidate gene and linkage designs, as well as genome-wide association (GWA) studies of common single-nucleotide polymorphisms (SNPs) and rare copy number variations (CNVs). Bioinformatic methods such as functional enrichment analysis and protein–protein network analysis are used to highlight biological processes of likely relevance to the aetiology of ADHD. Candidate gene associations of minor effect size have been replicated across a number of genes including SLC6A3 , DRD5 , DRD4 , SLC6A4 , LPHN3 , SNAP-25 , HTR1B , NOS1 and GIT1 . Although case-control SNP-GWAS have had limited success in identifying common genetic variants for ADHD that surpass critical significance thresholds, quantitative trait designs suggest promising associations with Cadherin13 and glucose–fructose oxidoreductase domain 1 genes. Further, CNVs mapped to glutamate receptor genes ( GRM1 , GRM5 , GRM7 and GRM8 ) have been implicated in the aetiology of the disorder and overlap with bioinformatic predictions based on ADHD GWAS SNP data regarding enriched pathways. Although increases in sample size across multi-center cohorts will likely yield important new results, we advocate that this must occur in parallel with a shift away from categorical case-control approaches that view ADHD as a unitary construct, towards dimensional approaches that incorporate endophenotypes and statistical classification methods.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Literature Review-2 ObjectType-Feature-3 ObjectType-Review-3 content type line 23
ISSN:	1359-4184 1476-5578 1476-5578
DOI:	10.1038/mp.2014.183