Common genetic variants underlying cognitive ability
07 / 2003 - 01 / 2008
Intelligence has been one of the most studied quantitative behavioral traits for more than 100 years. Psychometric intelligence tests consist of a number of component subtests that taken together are used to infer a general IQ (intelligence quotient) score. Previous twin studies have established that general IQ is influenced by genetic factors at all ages. Heritability estimates increase from around 30% in preschool children to 80% in early adolescence and adulthood. The stability of IQ performance during childhood is mainly driven by genetic influences. Therefore, if a trait is heritable, then the next step is to identify what causes this heritability. In order to identify common DNA polymorphisms explaining variation in cognitive ability, a family-based association study was conducted among a set of putative candidate genes. Two types of polymorphisms within a candidate-gene design were found associated with variation among cognitive ability phenotypes: coding or so-called functional polymorphisms (COMT and ADRB2 genes) and non-coding polymorphisms (CHRM2, SNAP-25, and DRD2 genes). While effects of the former type imply changes that can be observed at the protein level (i.e. enzymatic activity), the later type of polymorphisms should be considered as part of a wider range of regulatory elements, whose genetic contribution, although small in size, is necessary for the final phenotypic outcome. Future functional studies in combination with analysis of gene expression profiles at different brain regions may aid in understanding the role of genetic variants and their relation with synaptic plasticity underlying cognition, learning and attention traits.