Rare DNA variants in the brain-derived neurotrophic factor gene increase risk for attention-deficit hyperactivity disorder: a next-generation sequencing study

Attention-deficit hyperactivity disorder (ADHD) is a prevalent and highly heritable disorder of childhood with negative lifetime outcomes. Although candidate gene and genome-wide association studies have identified promising common variant signals, these explain only a fraction of the heritability o...

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Bibliographic Details
Published in:Molecular psychiatry 2017-04, Vol.22 (4), p.580-584
Main Authors: Hawi, Z, Cummins, T D R, Tong, J, Arcos-Burgos, M, Zhao, Q, Matthews, N, Newman, D P, Johnson, B, Vance, A, Heussler, H S, Levy, F, Easteal, S, Wray, N R, Kenny, E, Morris, D, Kent, L, Gill, M, Bellgrove, M A
Format: Article
Language:English
Subjects:
Adolescent
Attention Deficit Disorder with Hyperactivity - genetics
Attention deficit hyperactivity disorder
Autism
Brain research
Brain-derived neurotrophic factor
Brain-Derived Neurotrophic Factor - genetics
Brain-Derived Neurotrophic Factor - metabolism
Case-Control Studies
Child
Child & adolescent psychiatry
Children
DNA
Female
Gene mutation
Genes
Genetic aspects
Genetic Predisposition to Disease
Genetic Variation - genetics
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genotype
Heritability
High-Throughput Nucleotide Sequencing - methods
Humans
Hyperactivity
Ireland
Male
Mental disorders
Neurosciences
Next-generation sequencing
Polymorphism, Single Nucleotide - genetics
Risk Factors
Schizophrenia
Sequence Analysis, DNA - methods
Synaptic plasticity
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Description
Summary:Attention-deficit hyperactivity disorder (ADHD) is a prevalent and highly heritable disorder of childhood with negative lifetime outcomes. Although candidate gene and genome-wide association studies have identified promising common variant signals, these explain only a fraction of the heritability of ADHD. The observation that rare structural variants confer substantial risk to psychiatric disorders suggests that rare variants might explain a portion of the missing heritability for ADHD. Here we believe we performed the first large-scale next-generation targeted sequencing study of ADHD in 152 child and adolescent cases and 188 controls across an a priori set of 117 genes. A multi-marker gene-level analysis of rare (
ISSN:1359-4184
1476-5578
DOI:10.1038/mp.2016.117