A brilliant approach to study the basis of intelligence?
Genome-wide association studies have become powerful tools for investigating the genetic bases of several disorders. In order to understand the biological mechanisms that may contribute to disease prevention, recent studies have investigated the genetic profiles of individuals at the opposite end of the disease spectrum. For example, to identify therapeutic target to improve longevity, researchers are studying the unique genetics of centenarians. Using the same principle, Zabaneh et al. began to lay the ground work for understanding whether intellectual abilities are associated with genetic factors. By sequencing the genomes of ∼1200 individuals with extremely high IQ (mean IQ of ∼170, representing the top 0.0003 of the population) and comparing them with the general population, the researchers discovered genetic variants in locus ADAM12 that were linked to enhanced cognitive abilities and educational attainment. The ADAM12 gene encodes a disintegrin and metalloproteinase domain-containing (ADAM) protein, and members in this protein family have been implicated in cell-cell interactions and neurogenesis. Furthermore, subsequent pathway analysis revealed that the plexin gene family was enriched in the extreme IQ population. Plexins function as receptors for semaphorins and play a critical role in axon guidance and development. Altered plexin function has also been implicated in intellectual disability, suggesting that they might play a role in cognitive functions. Additional studies in which the function of plexins is directly manipulated in the central nervous system would clarify whether they play a causal relationship in establishing cognitive ability. Nevertheless, this study raises the intriguing possibility that studies targeting a few exceptional individuals may help to identify biological pathways that can be targeted to regulate cognitive functions in health and disease.
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