Family-based association of the brain-derived neurotrophic factor gene in attention-deficit hyperactivity disorder

Attention-deficit hyperactivity disorder (ADHD), a highly heritable neurodevelopmental disorder, is characterized by inattention and hyperactivity. The brain-derived neutotrophic factor (BDNF), a member of the neurotrophic factor family, is important for normal neuronal development. It has been proposed that BDNF may play a role in the therapeutic action and pathogenesis of ADHD (Tsai, 2003). A common single-nucleotide polymorphism (SNP) consisting of a missense change (G196A) that produces a nonconservative amino acid change (valine to methionine) has been identified in the coding exon of the BDNF gene at position 66 (Val66Met, rs6265). The replacement of Val66 by Met66 disrupts cellular processing, trafficking, and activity-dependent secretion of BDNF (Egan et al., 2003). Several association studies have tested the possible involvement of this BDNF Val66Met polymorphism in ADHD, although the results are controversial (Forero et al., 2009; Sanchez-Mora et al., 2010). To further clarify the role of BDNF in ADHD, we tested the hypothesis that the BDNF gene was associated with ADHD in Taiwanese families, using transmission disequilibrium analysis.