title: Voxelwise eigenvector centrality mapping of the human functional connectome reveals an influence of the catechol-O-methyltransferase val158met polymorphism on the default mode and somatomotor network.
abstract: Functional connections between brain regions constitute the substrate of the human functional connectome, whose topography has been discussed as an endophenotype for psychiatric disorders. Genetic influences on the entire connectome, however, have been rarely investigated so far. We tested for connectome-wide influences of the val158met (rs4860) polymorphism on the catechol-O-methyltransferase (COMT) gene by applying formal network analysis and eigenvector centrality mapping on the voxel level to resting-state functional magnetic imaging data. This approach finds brain regions that are central in the network by aggregating local and global connectivity patterns, most importantly without the requirement to select regions or networks of interest. The COMT variant linked to high enzyme activity increased network centrality in distributed brain areas that are known to constitute the brain's default mode network. Further results also indicated a COMT influence on areas implicated in the somatomotor network. These findings are in line with the polymorphism's alleged role in cognitive processing and its role in psychotic disorders. The study is the first to demonstrate the influence of a functional and behaviorally relevant genetic variant on connectome-wide functional connectivity and is an important step toward establishing the functional connectome as an endophenotype for psychiatric and behavioral phenotypes.
authors.affiliation: Department of Psychology, University of Bonn, Kaiser-Karl-Ring 9, 53111, Bonn, Germany. sebastian.markett@uni-bonn-diff.de.|Center for Economics and Neuroscience, University of Bonn, Bonn, Germany. sebastian.markett@uni-bonn-diff.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Markett
authors.affiliation: Department of Psychology, University of Ulm, Ulm, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Montag
authors.affiliation: Institute for Numerical Simulation, University of Bonn, Bonn, Germany.
authors.forename: Behrend
authors.initials: B
authors.lastname: Heeren
authors.affiliation: Department of Psychology, University of Ulm, Ulm, Germany.
authors.forename: Rayna
authors.initials: R
authors.lastname: Saryiska
authors.affiliation: Department of Psychology, University of Ulm, Ulm, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Lachmann
authors.affiliation: Center for Economics and Neuroscience, University of Bonn, Bonn, Germany.|Life and Brain Center Bonn, Bonn, Germany.|Department of Epileptology, University Clinics Bonn, Bonn, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Weber
authors.affiliation: Department of Psychology, University of Bonn, Kaiser-Karl-Ring 9, 53111, Bonn, Germany.|Center for Economics and Neuroscience, University of Bonn, Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reuter
mesh_terms: D000328:Adult; D001921:Brain / Q000502:physiology*; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000502:physiology*; D063132:Connectome / Q000379:methods*; D003627:Data Interpretation, Statistical; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009044:Motor Cortex / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D013003:Somatosensory Cortex / Q000502:physiology; D055815:Young Adult
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Catechol-O-methyltransferase; Default mode network; Functional connectivity; Functional connectome; Resting-state fMRI