title: Topology of genetic associations between regional gray matter volume and intellectual ability: Evidence for a high capacity network.
abstract: Intelligence is associated with a network of distributed gray matter areas including the frontal and parietal higher association cortices and primary processing areas of the temporal and occipital lobes. Efficient information transfer between gray matter regions implicated in intelligence is thought to be critical for this trait to emerge. Genetic factors implicated in intelligence and gray matter may promote a high capacity for information transfer. Whether these genetic factors act globally or on local gray matter areas separately is not known. Brain maps of phenotypic and genetic associations between gray matter volume and intelligence were made using structural equation modeling of 3T MRI T1-weighted scans acquired in 167 adult twins of the newly acquired U-TWIN cohort. Subsequently, structural connectivity analyses (DTI) were performed to test the hypothesis that gray matter regions associated with intellectual ability form a densely connected core. Gray matter regions associated with intellectual ability were situated in the right prefrontal, bilateral temporal, bilateral parietal, right occipital and subcortical regions. Regions implicated in intelligence had high structural connectivity density compared to 10,000 reference networks (p=0.031). The genetic association with intelligence was for 39% explained by a genetic source unique to these regions (independent of total brain volume), this source specifically implicated the right supramarginal gyrus. Using a twin design, we show that intelligence is genetically represented in a spatially distributed and densely connected network of gray matter regions providing a high capacity infrastructure. Although genes for intelligence have overlap with those for total brain volume, we present evidence that there are genes for intelligence that act specifically on the subset of brain areas that form an efficient brain network.
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: m.bohlken@umcutrecht.nl.
authors.forename: Marc M
authors.initials: MM
authors.lastname: Bohlken
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Brouwer
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: René C W
authors.initials: RCW
authors.lastname: Mandl
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Hedman
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Martijn P
authors.initials: MP
authors.lastname: van den Heuvel
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Neeltje E M
authors.initials: NEM
authors.lastname: van Haren
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Hilleke E
authors.initials: HE
authors.lastname: Hulshoff Pol
mesh_terms: D000328:Adult; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology; D001931:Brain Mapping; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000033:anatomy & histology* / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007360:Intelligence / Q000235:genetics* / Q000502:physiology*; D007361:Intelligence Tests; D008297:Male; D008957:Models, Genetic; D009415:Nerve Net / Q000033:anatomy & histology* / Q000502:physiology*; D010641:Phenotype; D014427:Twins; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
keywords: Connectivity; Gray matter; Heritability; Intelligence; Twin