A gene-brain-cognition pathway: Prefrontal activity mediates the effect of COMT on cognitive control and IQ

Adam E. Green, David J.M. Kraemer, Colin G. Deyoung, John A. Fossella, Jeremy R. Gray

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

A core thesis of cognitive neurogenetic research is that genetic effects on cognitive ability are mediated by specific neural functions, however, demonstrating neural mediation has proved elusive. Pairwise relationships between genetic variation and brain function have yielded heterogeneous findings to date. This heterogeneity indicates that a multiple mediator modeling approach may be useful to account for complex relationships involving function at multiple brain regions. This is relevant not only for characterizing healthy cognition but for modeling the complex neural pathways by which disease-related genetic effects are transmitted to disordered cognitive phenotypes in psychiatric illness. Here, in 160 genotyped functional magnetic resonance imaging participants, we used a multiple mediator model to test a gene-brain-cognition pathway by which activity in 4 prefrontal brain regions mediates the effects of catechol-O-methyltransferase (COMT) gene on cognitive control and IQ. Results provide evidence for gene-brain-cognition mediation and help delineate a pathway by which gene expression contributes to intelligence.

Original languageEnglish (US)
Pages (from-to)552-559
Number of pages8
JournalCerebral Cortex
Volume23
Issue number3
DOIs
StatePublished - Mar 2013

Bibliographical note

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • COMT
  • IQ
  • cognitive control
  • cognitive neurogenetics
  • fMRI

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