title: Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD.
abstract: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable, neurodevelopmental disorder with onset in early childhood. Genes involved in neuronal development and growth are, thus, important etiological candidates and brain-derived neurotrophic factor (BDNF), has been hypothesized to play a role in the pathogenesis of ADHD. BDNF is a member of the neurotrophin family and is involved in the survival and differentiation of dopaminergic neurons in the developing brain (of relevance because drugs that block the dopamine transporter can be effective therapeutically). The common Val66Met functional polymorphism in the human BDNF gene (rs 6265) was genotyped in a collaborative family-based sample of 341 white UK or Irish ADHD probands and their parents. We found evidence for preferential transmission of the valine (G) allele of BDNF (odds ratio, OR=1.6, P=0.02) with a strong paternal effect (paternal transmissions: OR=3.2, P=0.0005; maternal transmissions: OR=1.00; P=1.00). Our findings support the hypothesis that BDNF is involved in the pathogenesis of ADHD. The transmission difference between parents raises the possibility that an epigenetic process may be involved.
authors.affiliation: Developmental Psychiatry, University of Cambridge, Cambridge, UK. lk255@cam.ac.uk
authors.forename: L
authors.initials: L
authors.lastname: Kent
authors.forename: E
authors.initials: E
authors.lastname: Green
authors.forename: Z
authors.initials: Z
authors.lastname: Hawi
authors.forename: A
authors.initials: A
authors.lastname: Kirley
authors.forename: F
authors.initials: F
authors.lastname: Dudbridge
authors.forename: N
authors.initials: N
authors.lastname: Lowe
authors.forename: R
authors.initials: R
authors.lastname: Raybould
authors.forename: K
authors.initials: K
authors.lastname: Langley
authors.forename: N
authors.initials: N
authors.lastname: Bray
authors.forename: M
authors.initials: M
authors.lastname: Fitzgerald
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.forename: M C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: M
authors.initials: M
authors.lastname: Gill
authors.forename: A
authors.initials: A
authors.lastname: Thapar
authors.forename: N
authors.initials: N
authors.lastname: Craddock
mesh_terms: D019943:Amino Acid Substitution; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008715:Methionine; D008969:Molecular Sequence Data; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide; D014633:Valine
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D008715:Methionine; D014633:Valine