Charles Darwin, the renowned evolutionary biologist, wrote, “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.” Despite this assertion, human intelligence remains a fascinating and widely discussed topic. Intelligence is one of the most heritable traits in humans, with heritability estimates ranging from 25 to 40 percent in childhood and as high as 80 percent in adulthood.
Several studies have demonstrated the central role of the hippocampus in learning and memory. Damage to this brain region selectively impairs the ability to learn and remember. The gene for synaptosome-associated protein of 25 kDa (SNAP-25) is located in an area previously suggested to be an important link in intelligence and is highly expressed by neurons in the hippocampus. The SNAP-25 gene, located on chromosome 20p12–12p11.2, encodes a presynaptic terminal protein.
In the mature brain, the SNAP-25 gene product forms a complex with syntaxin and synaptic vesicle proteins that mediate the exocytosis of neurotransmitters from the synaptic vesicle into the synaptic cleft. Because of the important role of the SNAP-25 gene in learning and memory, which are two major components of intelligence, variants in this gene may influence individual differences in intelligence.
In this study, researchers conducted a family-based association study of two independent cohorts of children and adults to investigate whether the SNAP-25 gene plays a role in human intelligence. In total, 12 marker SNPs were selected for genotyping. In the youth cohort, cognitive ability was assessed with the Dutch adaptation of the Wechsler Intelligence Scale for Children-Revised and consisted of four verbal subtests (similarities, vocabulary, arithmetic, and digit span) and two performance subtests (block drawing and object assembly). In the adult cohort, the Dutch adaptation of the Wechsler Adult Intelligence Scale III-Revised assessed IQ and consisted of four verbal subtests (information, similarities, vocabulary, and arithmetic) and four performance subtests (picture completion, block drawing, matrix reasoning, and symbol substitution). The results showed that the G allele of rs363039 was significantly associated with higher performance IQ in the youth cohort (N=381) and in the combined analysis of the youth and adult cohorts (N=652). In the combined analysis, rs363039 also showed significant associations on both verbal IQ and full-scale IQ in the same direction of effect.
The rs363039 SNP was targeted in the 5’UTR region of the SNAP-25 gene in this study, and the researchers suggested that genetic variants located in this non-coding region may be regulating protein expression. These variants may influence regulatory binding sites, which in turn may modify gene expression and, consequently, the regulation of neurotransmitter release. A complex mechanism of subtle changes in fine-tuning at the level of the neurotransmitter release machinery, as well as in the interaction between neurotransmitter receptor subtypes, may affect individual differences in memory and learning.
