Myrum Craig, Giddaluru Sudheer, Jacobsen Kaya, Espeseth Thomas, Nyberg Lars, Lundervold Astri J, Haavik Jan, Nilsson Lars-Göran, Reinvang Ivar, Steen Vidar M, Johansson Stefan, Wibrand Karin, Le Hellard Stephanie, Bramham Clive R
Dr. Einar Martens Research Group for Biological Psychiatry Center for Medical Genetics and Molecular Medicine Haukeland University Hospital Bergen Norway ; Department of Biomedicine University of Bergen Bergen Norway ; K.G. Jebsen Center for Research on Neuropsychiatric Disorders University of Bergen Bergen Norway.
Dr. Einar Martens Research Group for Biological Psychiatry Center for Medical Genetics and Molecular Medicine Haukeland University Hospital Bergen Norway ; K.G. Jebsen Center for Psychosis Research and the Norwegian Center for Mental Disorders Research (NORMENT) Department of Clinical Science University of Bergen Bergen Norway.
Brain Behav. 2015 Sep 3;5(10):e00376. doi: 10.1002/brb3.376. eCollection 2015 Oct.
The Activity-Regulated Cytoskeleton-associated (ARC) gene encodes a protein that is critical for the consolidation of synaptic plasticity and long-term memory formation. Given ARC's key role in synaptic plasticity, we hypothesized that genetic variations in ARC may contribute to interindividual variability in human cognitive abilities or to attention-deficit hyperactivity disorder (ADHD) susceptibility, where cognitive impairment often accompanies the disorder.
We tested whether ARC variants are associated with six measures of cognitive functioning in 670 healthy subjects in the Norwegian Cognitive NeuroGenetics (NCNG) by extracting data from its Genome-Wide Association Study (GWAS). In addition, the Swedish Betula sample of 1800 healthy subjects who underwent similar cognitive testing was also tested for association with 19 tag SNPs.
No ARC variants show association at the study-wide level, but several markers show a trend toward association with human cognitive functions. We also tested for association between ARC SNPs and ADHD in a Norwegian sample of cases and controls, but found no significant associations.
This study suggests that common genetic variants located in ARC do not account for variance in human cognitive abilities, though small effects cannot be ruled out.
活性调节细肌丝相关蛋白(ARC)基因编码一种蛋白质,该蛋白质对于突触可塑性的巩固和长期记忆形成至关重要。鉴于ARC在突触可塑性中的关键作用,我们推测ARC基因的遗传变异可能导致人类认知能力的个体差异或注意力缺陷多动障碍(ADHD)易感性,而认知障碍常伴随该疾病。
我们通过从挪威认知神经遗传学(NCNG)的全基因组关联研究(GWAS)中提取数据,测试了ARC变异是否与670名健康受试者的六种认知功能指标相关。此外,对1800名接受类似认知测试的瑞典桦木样本健康受试者也进行了与19个标签单核苷酸多态性(SNP)的关联测试。
在全研究水平上,没有ARC变异显示出相关性,但有几个标记显示出与人类认知功能相关的趋势。我们还在挪威的病例和对照样本中测试了ARC SNP与ADHD之间的关联,但未发现显著关联。
本研究表明,ARC中常见的遗传变异不能解释人类认知能力的差异,尽管不能排除微小效应。