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Rare DNA variants in the brain derived neurotrophic factor gene increase risk for attention deficit hyperactivity disorder : a next generation sequencing study
- Publication Year :
- 2017
-
Abstract
- This work was supported by a grant from the National Health and Medical Research Council of Australia (NHMRC) (APP1065677). 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 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 (< 1% frequency) single nucleotide variants (SNVs) revealed that the gene encoding brain derived neurotrophic factor (BDNF) was associated with ADHD at Bonferroni corrected levels. Sanger sequencing confirmed the existence of all novel rare BDNF variants. Our results implicate BDNF as a genetic risk factor for ADHD, potentially by virtue of its critical role in neurodevelopment and synaptic plasticity. Postprint
- Subjects :
- 0301 basic medicine
Male
Candidate gene
Adolescent
Genotype
Genome-wide association study
QH426 Genetics
Polymorphism, Single Nucleotide
03 medical and health sciences
Cellular and Molecular Neuroscience
symbols.namesake
Missing heritability problem
Risk Factors
medicine
Attention deficit hyperactivity disorder
Humans
Genetic Predisposition to Disease
Child
Molecular Biology
QH426
Genetic association
Genetics
Sanger sequencing
Brain-derived neurotrophic factor
Brain-Derived Neurotrophic Factor
Genetic Variation
High-Throughput Nucleotide Sequencing
DAS
DNA
Sequence Analysis, DNA
medicine.disease
Psychiatry and Mental health
030104 developmental biology
Schizophrenia
Attention Deficit Disorder with Hyperactivity
Case-Control Studies
symbols
RC0321
Female
Psychology
Neuroscience
Ireland
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....efb0c6f4a2bdef1202ea5cc6a7d9b1ef