Cognitive Ability and Homozygosity Study

Recent studies of genetic foundations of cognitive ability rely on large samples (hundreds of thousands) of individuals from relatively outbred populations of mostly European ancestry. Hypothesizing that the genetic foundation of cognitive ability depends on the broader population-specific genetic context, we performed a genome-wide association study and homozygosity mapping of cognitive ability estimates obtained through latent variable modeling in a sample of 354 children from the consanguineous population of Saudi Arabia. Approximately half of the sample demonstrated significantly elevated homozygosity levels indicative of inbreeding, and among those with elevated homozygosity, it was negatively associated with cognitive ability. Further homozygosity mapping identified a specific run, inclusive of the GRIA4 gene, that survived corrections for multiple testing for association with cognitive ability. The results suggest that in a consanguineous population, a notable proportion of the variance in cognitive ability in the normal range in children might be regulated by population-specific mechanisms such as patterns of elevated autozygosity.]]>
Linear mixed modeling approach was used to establish SNP-level associations for cognitive ability. Phenotypic variable was residualized for a set of covariates within a robust linear mixed modeling framework prior to analysis. Linear mixed modeling approach was used to establish SNP-level associations for cognitive ability. Phenotypic variable was residualized for a set of covariates within a robust linear mixed modeling framework prior to analysis. Linear mixed modeling approach was used to establish SNP-level associations for cognitive ability. Phenotypic variable was residualized for a set of covariates within a robust linear mixed modeling framework prior to analysis. Linear mixed modeling approach was used to establish SNP-level associations for cognitive ability. Phenotypic variable was residualized for a set of covariates within a robust linear mixed modeling framework prior to analysis. A small proportion of children were nominated by their teachers for the genetic study based on a) high levels of cognitive ability, and b) Saudi-Arabian ancestry. The initial pool of probands with high cognitive ability was constructed through the selection of n=942 children by local school officials as representing the top 15% of performers on all of the standardized intelligence assessment items (the Aurora assessment battery) within each grade. Saliva was collected from every consenting proband (n=354).]]>
All children were administered a paper-and-pencil intelligence assessment in a group format in a controlled school environment after providing saliva samples. Participants for the genetic study were recruited from a larger sample enrolled in an epidemiological study of cognitive ability in children in Saudi Arabia. A total of n=7,186 children in the age range from 7.34 to 18.71 years (M = 12.28, SD = 1.81; 4,682 males and 2,504 females) were recruited from local schools in seven major regions of Saudi Arabia: Abha (n=605), Khamis-Mushyat (n=585), Tabuk (n=1,095), Al-Jubail (n=1,004), Jeddah (n=2,272), and Al-Hassa (n=1,625) for that study.]]>