Association study of brain-derived neurotrophic factor (BDNF) and LIN-7 homolog (LIN-7) genes with adult attention-deficit/hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder with a large genetic component that has been shown to persist into adulthood in 30-60% of childhood ADHD cases. Adult ADHD confers an increased risk of ADHD in relatives when compared to childhood ADHD, possibly due to a greater genetic liability than the childhood form. Brain-derived neurotrophic factor (BDNF) is a neurotrophin expressed in the brain throughout life and is involved in survival, differentiation, and synaptic plasticity of several neuronal systems including dopaminergic pathways. Mammalian LIN-7 homolog is selectively expressed in specific neuronal populations and is involved in the postsynaptic density of neuronal synapses. LIN-7 is also a positional candidate, as it lies immediately downstream of BDNF. We tested for association between five BDNF polymorphisms, two LIN-7 polymorphisms and adult ADHD. The sample consisted of 80 trios comprised of an adult ADHD proband and their biological parents and an independent sample of 121 adult ADHD cases and a corresponding number of sex, age, and ethnically matched controls (total 201 probands). Allelic and haplotype association was found between both BDNF and adult ADHD, and LIN-7 and adult ADHD. HapMap indicates BDNF and LIN-7 occur in different haplotype blocks, though some linkage disequilibrium exists between the SNPs in these adjacent genes. Further investigations into the pathologic mechanisms of BDNF and LIN-7 in adult ADHD are required.
Lanktree
Matthew
M
Neurogenetics Section, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
Squassina
Alessio
A
Krinsky
Marilee
M
Strauss
John
J
Jain
Umesh
U
Macciardi
Fabio
F
Kennedy
James L
JL
Muglia
Pierandrea
P
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D033921:Vesicular Transport Proteins
D048868:Adaptor Proteins, Signal Transducing; D019208:Brain-Derived Neurotrophic Factor; C486532:LIN7A protein, human; C114671:LIN7B protein, human; C486531:LIN7C protein, human; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins