title: Association study of the brain-derived neurotropic factor (BDNF) gene in attention deficit hyperactivity disorder.
abstract: Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental childhood psychiatric disorder. Brain-derived neurotropic factor (BDNF) has been suggested to play a role in the pathogenesis of ADHD and two family-based association studies demonstrated an association of BDNF polymorphisms with ADHD. The aim of the current study was to investigate the BDNF gene for association with ADHD in a large sample of families from Toronto. The transmission of three polymorphisms of the BDNF gene (rs6265, rs11030104, and rs2049046) was examined in 266 nuclear families ascertained through a proband with ADHD (315 affected children) using the transmission/disequilibrium test (TDT). In addition, we conducted quantitative analysis to assess the relationship between these marker alleles and the symptom dimensions of ADHD (inattention and hyperactivity/impulsivity) and cognitive measures of working memory. None of the individual marker alleles showed significant evidence of association with ADHD, dimensional symptom scores, or working memory ability in our sample of ADHD families. There was no significant evidence for biased transmission of individual haplotypes with frequency >10% (global chi2 for these three haplotypes: chi2 = 6.349, df = 3, P = 0.096). One uncommon haplotype (A-G-G; frequency 2.2%) showed a significant association with ADHD in the categorical (chi2 = 5.293, df = 1, P = 0.021) and quantitative analyses (parents' rated inattention: Z = -2.504, P = 0.012; and hyperactivity/impulsivity: Z = -2.651, P = 0.008). These results should be interpreted cautiously, however, because of the low haplotype frequency. In light of the evidence for an involvement of BDNF in ADHD, further analysis of the BDNF gene in ADHD is warranted.
authors.affiliation: Cell and Molecular Biology Division, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Jonghun
authors.initials: J
authors.lastname: Lee
authors.forename: Nancy
authors.initials: N
authors.lastname: Laurin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Crosbie
authors.forename: Abel
authors.initials: A
authors.lastname: Ickowicz
authors.forename: Tejaswee
authors.initials: T
authors.lastname: Pathare
authors.forename: Molly
authors.initials: M
authors.lastname: Malone
authors.forename: Rosemary
authors.initials: R
authors.lastname: Tannock
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Russell
authors.initials: R
authors.lastname: Schachar
authors.forename: Cathy L
authors.initials: CL
authors.lastname: Barr
mesh_terms: D000293:Adolescent; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D035781:Siblings
chemical_list: D019208:Brain-Derived Neurotrophic Factor