A Quantitative Trait Locus Associated With Cognitive Ability in Children

Abstract

Quantitative trait loci (QTLs) associated with general cognitive ability ( g) were investigated for several groups of children selected for very high or for average cognitive functioning. A DNA marker in the gene for insulin-like growth factor-2 receptor (IGF2R) on Chromosome 6 yielded a significantly greater frequency of a particular form of the gene (allele) in a high- g group (.303; average IQ = 136, N = 51) than in a control group (.156; average IQ = 103, N = 51). This association was replicated in an extremely-high- g group (all estimated IQs > 160, N = 52) as compared with an independent control group (average IQ = 101, N = 50), with allelic frequencies of .340 and .169, respectively. Moreover, a high-mathematics-ability group ( N = 62) and a high-verbal-ability group ( N = 51) yielded results that were in the same direction but only marginally significant ( p = .06 and .08, respectively).

Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population

“…The previous finding that IGF2R 6 is associated with intelligence and is also responsible for the transport of CTSD helps validate our result and suggests that the successful transport of CTSD is an important step for the optimal development of the human brain. Screening of both genes for new exonic and regulatory polymorphisms will be our next priority.…”

“…A microsatellite at the 3 0 end of the IGF2R gene contains a variable number of repeats that have been shown to be associated with children's IQ. 6 Other loci that have previously been associated with intelligence include a microsatellite polymorphism within the MSX1 gene located on chromosome 4 and two other microsatellite markers (D4S2943 and D4S1607) that are also located on chromosome 4. 7 Cathepsin D (CTSD) is an active acid protease that is initially produced as a nonfunctional enzyme in the trans Golgi network.…”

Genetics, genes, genomics and g

“…44 This is of particular concern with studies using unselected samples because it is tempting to study many measures as well as many candidate genes thus increasing vulnerability to false positives. As a chastening confession to underline the need for replication, both papers cite our report of an association between IGF2R and g in two samples, 45 but our new independent sample as large as the previous two samples combined has not replicated the association. 46 Other molecular genetic issues relevant to these CTSD and CHRM2 reports are generic issues involved in any attempt to find QTLs for complex traits whether assessed as disorders or dimensions.…”

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

“…Using eight of the most significant markers associated with general cognitive ability (g), associations were confirmed for spatial, verbal and memory abilities, implying that there was some overlap in genetic effects on specific abilities and g (Petrill et al, 1996b). A more systematic approach was later taken by using a denser map of markers, subjects with a wider IQ range, and replication samples to reduce Type I errors; the first replicated association was between g and the insulin-like growth factor-2 receptor (IGRF) gene (Chorney et al, 1998), although this did not generalise to an independent sample (2001). In a genomewide association analysis using 1842 markers, Plomin and colleagues (2001) found associations with 108 markers in the first stage of analysis (case-control DNA pooling), but none replicated to all five stages.…”