From Rare Mutations to Normal Variation: Genetic Association Study of Mathematical, Spatial, and General Cognitive Abilities

Background. Behavioral genetic findings suggest that complex traits, such as mathematical ability, general cognitive ability (intelligence; g), and spatial ability, are influenced by many common genetic variants of very small effects that operate across the ability continuum. Common genetic variants may also be responsible for cognitive deficits associated with rare genetic syndromes, in which whole genomic regions may be affected. To date, relatively few common genetic variants involved in cognitive traits have been identified, and these only explain a small proportion of variance in these traits. Objective. The aim of the study was to find associations between mathematics-related traits and single-nucleotide polymorphisms (SNPs) within chromosomal regions involved in Williams and Prader-Willi disorders. Both disorders are characterized by patterns of weaknesses and strengths in cognitive abilities. Two types of analyses were performed (SNP-based and gene-based), using genotypic and phenotypic data available for 3000 participants from the UK. Results. SNP-based tests indicated that none of the SNPs passed the demanding multiple testing correction level for any of the phenotypes. Gene-based analysis suggested that 2 pseudogenes (i.e., GOLGA8I and WHAMMP3) were significantly associated with intelligence, and 1 gene (i.e., TUBGCP5) was significantly associated with mathematics at 16 years of age. Conclusion. The results are consistent with other findings demonstrating that cognitive traits are influenced by many common genetic variants with very small effects. The results also suggest that a small number of these variants may be located in the chromosomal regions affected in Prader-Willi and Williams syndrome regions.