Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence
- 11 December 2019
- journal article
- research article
- Published by Oxford University Press (OUP) in Cerebral Cortex
- Vol. 30 (4), 2708-2719
- https://doi.org/10.1093/cercor/bhz270
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.Funding Information
- German Ministry for Education and Research (01GS08148)
- e:Med (O1ZX1314B, O1ZX1314G)
- Forschungsnetz AERIAL (01EE1406A, 01EE1406B)
- NARSAD
- BMBF (01EE1407)
- DFG (Wa 1539/11–1, ER 724/4–1)
- IMAGEN (LSHM-CT-2007-037286)
- ERC (695313)
- ERANID (PR-ST-0416-10004)
- BRIDGET (MR/N027558/1)
- IMAGEMEND (602450)
- MATRICS (603016)
- Innovative Medicine Initiative (115300–2)
- Medical Research Council (MR/N000390/1)
- Swedish Research Council Formas
- Medical Research Council
- National Institute for Health Research
- Bundesministeriumfür Bildung und Forschung (01GS08152, 01EV0711, eMED SysAlc01ZX1311A, 01EE1406A, 01EE1406B)
- Deutsche Forschungsgemeinschaft (SM 80/7–2, SFB 940/2)
- Medical Research Foundation (MR/R00465X/1)
- ANR (AF12-NEUR0008–01—WM2NA, ANR-12-SAMA-0004)
- Fondation pour la Recherche Médicale (DPA20140629802)
- Science Foundation Ireland (16/ERCD/3797, RO1 MH085772-01A1)
- NIH (U54 EB020403)
This publication has 82 references indexed in Scilit:
- GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational AttainmentScience, 2013
- Correction: Power and Predictive Accuracy of Polygenic Risk ScoresPLoS Genetics, 2013
- Power and Predictive Accuracy of Polygenic Risk ScoresPLoS Genetics, 2013
- COGNITIVE DEFICITS AND FUNCTIONAL OUTCOMES IN MAJOR DEPRESSIVE DISORDER: DETERMINANTS, SUBSTRATES, AND TREATMENT INTERVENTIONSDepression and Anxiety, 2013
- Genome-wide association studies establish that human intelligence is highly heritable and polygenicMolecular Psychiatry, 2011
- Cortical thickness correlates of specific cognitive performance accounted for by the general factor of intelligence in healthy children aged 6 to 18NeuroImage, 2011
- Cortical thickness or grey matter volume? The importance of selecting the phenotype for imaging genetics studiesNeuroImage, 2010
- The role of general intelligence as an intermediate phenotype for neuropsychiatric disordersCognitive Neuropsychiatry, 2009
- The heritability of general cognitive ability increases linearly from childhood to young adulthoodMolecular Psychiatry, 2009
- Distinct Genetic Influences on Cortical Surface Area and Cortical ThicknessCerebral Cortex, 2009