BACKGROUND: Working memory (WM) is the ability to retain task relevant information. This ability is important for a wide range of cognitive tasks, and WM deficits are a central cognitive impairment in neurodevelopment disorders such as attention-deficit/hyperactivity disorder (ADHD). Although WM capacity is known to be highly heritable, most genes involved remain unidentified. METHODS: Single nucleotide polymorphisms in genes previously associated with cognitive functions or ADHD were selected for genotyping. Associations of these with WM tasks were investigated in a community sample of 330 children and young adults. One single nucleotide polymorphisms was also investigated in an independent sample of 88 4-year-old children. Furthermore, association between brain structure and activity, as measured by magnetic resonance imaging techniques, and single nucleotide polymorphisms alleles were estimated in 88 participants. RESULTS: Genotype at rs363039, located in the gene coding for synaptosomal-associated protein, 25 kDa (SNAP25) was associated to WM capacity in both samples. Associations in the community sample were also found with measures of other cognitive functions. In addition, this polymorphism affected the gray matter and brain activity in the posterior cingulate cortex, an area included in the so-called default mode network previously correlated to regulation of attention and hypothesized to be implicated in ADHD. CONCLUSIONS: A novel gene-brain-behavior network was identified in which a genotype located in SNAP25 affects WM and has age-dependent effects on both brain structure and brain activity. Identifying such networks could be a key to better understanding cognitive development as well as some of its disorders.
BACKGROUND:Working memory (WM) is the ability to retain task relevant information. This ability is important for a wide range of cognitive tasks, and WM deficits are a central cognitive impairment in neurodevelopment disorders such as attention-deficit/hyperactivity disorder (ADHD). Although WM capacity is known to be highly heritable, most genes involved remain unidentified. METHODS: Single nucleotide polymorphisms in genes previously associated with cognitive functions or ADHD were selected for genotyping. Associations of these with WM tasks were investigated in a community sample of 330 children and young adults. One single nucleotide polymorphisms was also investigated in an independent sample of 88 4-year-old children. Furthermore, association between brain structure and activity, as measured by magnetic resonance imaging techniques, and single nucleotide polymorphisms alleles were estimated in 88 participants. RESULTS: Genotype at rs363039, located in the gene coding for synaptosomal-associated protein, 25 kDa (SNAP25) was associated to WM capacity in both samples. Associations in the community sample were also found with measures of other cognitive functions. In addition, this polymorphism affected the gray matter and brain activity in the posterior cingulate cortex, an area included in the so-called default mode network previously correlated to regulation of attention and hypothesized to be implicated in ADHD. CONCLUSIONS: A novel gene-brain-behavior network was identified in which a genotype located in SNAP25 affects WM and has age-dependent effects on both brain structure and brain activity. Identifying such networks could be a key to better understanding cognitive development as well as some of its disorders.