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The Journal of Neuroscience, October 4, 2006, 26(40):10235-10242; doi:10.1523/JNEUROSCI.1312-06.2006

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Behavioral/Systems/Cognitive
Genetic Contributions to Human Brain Morphology and Intelligence

Hilleke E. Hulshoff Pol,¹ Hugo G. Schnack,¹ Danielle Posthuma,² René C. W. Mandl,¹ Wim F. Baaré,¹ Clarine van Oel,¹ Neeltje E. van Haren,¹ D. Louis Collins,³ Alan C. Evans,³ Katrin Amunts,^4,5 Uli Bürgel,^6,7 Karl Zilles,^4,7 Eco de Geus,² Dorret I. Boomsma,² and René S. Kahn¹

¹Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands, ²Department of Biological Psychology, Free University Amsterdam, 1081 BT Amsterdam, The Netherlands, ³Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4, ⁴Institut fuer Medizin, Forschungszentrum Juelich, D-52405 Juelich, Germany, Departments of ⁵Psychotherapy and Psychiatry and ⁶Neurosurgery, Die Leitseite der Rheinisch-Westfälischen Technischen Hochschule Aachen University, D-52062 Aachen, Germany, and ⁷C. and O. Vogt Institute for Brain Research, Heine University Düsseldorf, D-40225 Düsseldorf, Germany

Correspondence should be addressed to Dr. Hilleke E. Hulshoff Pol, University Medical Center Utrecht, Heidelberglaan 100, Department of Psychiatry, A01.126, 3584 CX Utrecht, The Netherlands. Email: h.e.hulshoff{at}azu.nl

Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology of specific GM areas in the brain have been studied, the heritability of focal WM is unknown. Similarly, it is unresolved whether there is a common genetic origin of focal GM and WM structures with intelligence. We explored the genetic influence on focal GM and WM densities in magnetic resonance brain images of 54 monozygotic and 58 dizygotic twin pairs and 34 of their siblings. For genetic analyses, we used structural equation modeling and voxel-based morphometry. To explore the common genetic origin of focal GM and WM areas with intelligence, we obtained cross-trait/cross-twin correlations in which the focal GM and WM densities of each twin are correlated with the psychometric intelligence quotient of his/her cotwin. Genes influenced individual differences in left and right superior occipitofrontal fascicle (heritability up to 0.79 and 0.77), corpus callosum (0.82, 0.80), optic radiation (0.69, 0.79), corticospinal tract (0.78, 0.79), medial frontal cortex (0.78, 0.83), superior frontal cortex (0.76, 0.80), superior temporal cortex (0.80, 0.77), left occipital cortex (0.85), left postcentral cortex (0.83), left posterior cingulate cortex (0.83), right parahippocampal cortex (0.69), and amygdala (0.80, 0.55). Intelligence shared a common genetic origin with superior occipitofrontal, callosal, and left optical radiation WM and frontal, occipital, and parahippocampal GM (phenotypic correlations up to 0.35). These findings point to a neural network that shares a common genetic origin with human intelligence.

Key words: genetics; twins; neuroanatomy; voxel-based morphometry; intelligence; cognition

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Received Oct. 11, 2005; revised July 20, 2006; accepted July 21, 2006.

Correspondence should be addressed to Dr. Hilleke E. Hulshoff Pol, University Medical Center Utrecht, Heidelberglaan 100, Department of Psychiatry, A01.126, 3584 CX Utrecht, The Netherlands. Email: h.e.hulshoff{at}azu.nl

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