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

• DOI: 10.1038/sj.mp.4001696
• Publication Date: 2005-06-07T15:02:38Z
• Authors: L Kent; E Green; Z Hawi; A Kirley; F Dudbridge; N Lowe; R Raybould; K Langley; N Bray; M Fitzgerald; M J Owen; M C O'Donovan; M Gill; A Thapar; N Craddock
• Keywords: Male; Molecular Sequence Data; 2804 Cellular and Molecular Neuroscience; 610; Neurotrophic factor; Polymorphism, Single Nucleotide; Nuclear Family; Attention deficit hyperactivity disorder; 03 medical and health sciences; Methionine; 2738 Psychiatry and Mental health; 616; 1312 Molecular Biology; Humans; Genetic Predisposition to Disease; Polymorphism; DNA Primers; 0303 health sciences; Base Sequence; Brain-Derived Neurotrophic Factor; Valine; Association study; Amino Acid Substitution; Attention Deficit Disorder with Hyperactivity; Female

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.