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

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.