The SNAP-25 gene is associated with cognitive ability: evidence from a family-based study in two independent Dutch cohorts

Abstract

The synaptosomal-associated protein of 25 kDa (SNAP-25) gene plays an integral role in synaptic transmission, and is differentially expressed in the mammalian brain in the neocortex, hippocampus, anterior thalamic nuclei, substantia nigra and cerebellar granular cells. Recent studies have suggested a possible involvement of SNAP-25 in learning and memory, both of which are key components of human intelligence. In addition, the SNAP-25 gene lies in a linkage area implicated previously in human intelligence. In two independent family-based Dutch samples of 391 (mean age 12.4 years) and 276 (mean age 37.3 years) subjects, respectively, we genotyped 12 single-nucleotide polymorphisms (SNPs) in the SNAP-25 gene on 20p12-20p11.2. From all individuals, standardized intelligence measures were available. Using a family-based association test, a strong association was found between three SNPs in the SNAP-25 gene and intelligence, two of which showed association in both independent samples. The strongest, replicated association was found between SNP rs363050 and performance IQ (PIQ), where the A allele was associated with an increase of 2.84 PIQ points (P = 0.0002). Variance in this SNP accounts for 3.4 % of the phenotypic variance in PIQ.

A Functional Polymorphism under Positive Evolutionary Selection in ADRB2 is Associated with Human Intelligence with Opposite Effects in the Young and the Elderly

“…The derived, human specific allele in the beta-2 adrenergic receptor (rs1042713) is known to reduce agonist induced down-regulation of receptor density and was found to increase cognitive ability in the young Dutch cohort but was associated with a decrease in the Scottish cohort at age 70. The contrasting results for the age groups *12, *37 and 70 years for this functional variant are similar to the effect of a mutation in the brain-derived neurotrophic factor shown to be associated with age-related change in reasoning skills (Harris et al 2006) and might be explained by the observation that different age classes are known to differ in the genetic architecture of cognitive ability reflected in different heritability estimates (see Gosso et al 2006). A similar shift in monoaminergic neurotransmission with ageing is seen for dopaminergic systems regulated by catechol-O-methyltransferase.…”

“…The QTDT software package was used to perform a family-based association analysis in two Dutch cohorts phenotyped for several measures of cognitive ability (for details see below and Gosso et al 2006). IQ data were corrected for age and sex, and all analyses were performed while modeling the environmental and (poly-) genetic components of variance.…”

Catechol O-methyl transferase and dopamine D2 receptor gene polymorphisms: evidence of positive heterosis and gene–gene interaction on working memory functioning

“…Results on cognitive effects of two other genes are described elsewhere. 39,40 Statistical analyses Allele frequencies of the COMT Val 108/158 Met and DRD2 A1/A2 polymorphisms were estimated in both cohorts using Haploview (http://www.broad. mit.edu/mpg/haploview), in which a Hardy -Weinberg test is implemented, based on an exact calculation of the probability of observing a certain number of heterozygotes conditional on the number of copies of the minor SNP allele.…”

SNAP-25 genotype influences NAA/Cho in left hippocampus

“…This SNAP-25 modulated mechanism might influence the hippocampal function. It is possible, therefore, that the reported association of SNAP-25 genotype with memory consolidation (Hou et al 2004) and long-term memory formation (Hou et al 2006) in rats as well as cognitive ability in humans (Gosso et al 2006) is caused by its influence on hippocampal function.…”

“…Furthermore, animal studies showed that the hippocampal SNAP-25 protein is involved in memory consolidation and long-term memory formation in rats (Hou et al 2004(Hou et al , 2006. In humans it has been shown recently that the SNAP-25 gene is associated with the cognitive ability of healthy individuals (Gosso et al 2006). …”