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Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence.

ABSTRACT: Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived polygenic scores for intelligence (PSi) and g-factor. Using the effect sizes from one of the largest GWAS meta-analysis on general intelligence to date, PSi were calculated among 10 P value thresholds. PSi were assessed for the association with g-factor performance, cortical thickness (CT), and surface area (SA) in two large imaging-genetics samples (IMAGEN N = 1651; IntegraMooDS N = 742). PSi explained up to 5.1% of the variance of g-factor in IMAGEN (F1,1640 = 12.2-94.3; P < 0.005), and up to 3.0% in IntegraMooDS (F1,725 = 10.0-21.0; P < 0.005). The association between polygenic scores and g-factor was partially mediated by SA and CT in prefrontal, anterior cingulate, insula, and medial temporal cortices in both samples (PFWER-corrected < 0.005). The variance explained by mediation was up to 0.75% in IMAGEN and 0.77% in IntegraMooDS. Our results provide evidence that cumulative genetic load influences g-factor via cortical structure. The consistency of our results across samples suggests that cortex morphology could be a novel potential biomarker for neurocognitive dysfunction that is among the most intractable psychiatric symptoms.

SUBMITTER: Lett TA

PROVIDER: S-EPMC7175009 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Neuroimaging research indicates that human intellectual ability is related to brain structure including the thickness of the cerebral cortex. Most studies indicate that general intelligence is positively associated with cortical thickness in areas of association cortex distributed throughout both brain hemispheres. In this study, we performed a cortical thickness mapping analysis on data from 182 healthy typically developing males and females ages 9 to 24 years to identify correlates of general intelligence (g) scores. To determine if these correlates also mediate associations of specific cognitive abilities with cortical thickness, we regressed specific cognitive test scores on g scores and analyzed the residuals with respect to cortical thickness. The effect of age on the association between cortical thickness and intelligence was examined. We found a widely distributed pattern of positive associations between cortical thickness and g scores, as derived from the first unrotated principal factor of a factor analysis of Wechsler Abbreviated Scale of Intelligence (WASI) subtest scores. After WASI specific cognitive subtest scores were regressed on g factor scores, the residual score variances did not correlate significantly with cortical thickness in the full sample with age covaried. When participants were grouped at the age median, significant positive associations of cortical thickness were obtained in the older group for g-residualized scores on Block Design (a measure of visual-motor integrative processing) while significant negative associations of cortical thickness were observed in the younger group for g-residualized Vocabulary scores. These results regarding correlates of general intelligence are concordant with the existing literature, while the findings from younger versus older subgroups have implications for future research on brain structural correlates of specific cognitive abilities, as well as the cognitive domain specificity of behavioral performance correlates of normative gray matter thinning during adolescence.

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Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence.

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