Cortical surfaces mediate the relationship between polygenic scores for intelligence and general intelligence

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Charité – Universitätsmedizin Berlin
  • Massachusetts General Hospital
  • Broad Institute of Harvard University and MIT
  • University of Bonn
  • Heidelberg University 
  • Trinity College Dublin
  • University of Hamburg
  • King's College London (KCL)
  • University of Mannheim
  • French Alternative Energies and Atomic Energy Commission (CEA)
  • University of Vermont
  • University of Nottingham
  • Physikalisch-Technische Bundesanstalt
  • INSERM - Institut national de la santé et de la recherche médicale
  • Maison de Solenn
  • Sorbonne Université
  • Bloorview Research Institute
  • University of Göttingen

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.

Details

Original languageEnglish
Pages (from-to)2708-2719
Number of pages12
JournalCerebral cortex
Volume30
Issue number4
Publication statusE-pub ahead of print - 11 Dec 2019
Peer-reviewedYes

External IDs

PubMed 31828294
ORCID /0000-0002-8493-6396/work/161409523
ORCID /0000-0001-5398-5569/work/161409052

Keywords

Keywords

  • Cortical thickness, Genetics, Intelligence, Mediation, Surface area

Library keywords