Association study of brain‐derived neurotrophic factor (BDNF) and LIN‐7 homolog (LIN‐7) genes with adult attention‐deficit/hyperactivity disorder

Abstract

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.