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The Journal of Neuroscience, February 18, 2009, 29(7):2212-2224; doi:10.1523/JNEUROSCI.4184-08.2009

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Behavioral/Systems/Cognitive
Genetics of Brain Fiber Architecture and Intellectual Performance

Ming-Chang Chiang,¹ Marina Barysheva,¹ David W. Shattuck,¹ Agatha D. Lee,¹ Sarah K. Madsen,¹ Christina Avedissian,¹ Andrea D. Klunder,¹ Arthur W. Toga,¹ Katie L. McMahon,² Greig I. de Zubicaray,² Margaret J. Wright,³ Anuj Srivastava,⁴ Nikolay Balov,⁴ and Paul M. Thompson¹

¹Laboratory of Neuro Imaging, Department of Neurology, University of California, Los Angeles, School of Medicine, Los Angeles, California 90095-7334, ²University of Queensland, Functional Magnetic Resonance Imaging Laboratory, Centre for Magnetic Resonance, Brisbane, Queensland 4072, Australia, ³Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia, and ⁴Department of Statistics, Florida State University, Tallahassee, Florida 32306

Correspondence should be addressed to Dr. Paul M. Thompson, Laboratory of Neuro Imaging, Department of Neurology, University of California, Los Angeles, School of Medicine, 635 Charles E. Young Drive South, Suite 225E, Los Angeles, CA 90095-7334. Email: thompson{at}loni.ucla.edu

The study is the first to analyze genetic and environmental factors that affect brain fiber architecture and its genetic linkage with cognitive function. We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4 Tesla), in 92 identical and fraternal twins. White matter integrity, quantified using fractional anisotropy (FA), was used to fit structural equation models (SEM) at each point in the brain, generating three-dimensional maps of heritability. We visualized the anatomical profile of correlations between white matter integrity and full-scale, verbal, and performance intelligence quotients (FIQ, VIQ, and PIQ). White matter integrity (FA) was under strong genetic control and was highly heritable in bilateral frontal (a² = 0.55, p = 0.04, left; a² = 0.74, p = 0.006, right), bilateral parietal (a² = 0.85, p < 0.001, left; a² = 0.84, p < 0.001, right), and left occipital (a² = 0.76, p = 0.003) lobes, and was correlated with FIQ and PIQ in the cingulum, optic radiations, superior fronto-occipital fasciculus, internal capsule, callosal isthmus, and the corona radiata (p = 0.04 for FIQ and p = 0.01 for PIQ, corrected for multiple comparisons). In a cross-trait mapping approach, common genetic factors mediated the correlation between IQ and white matter integrity, suggesting a common physiological mechanism for both, and common genetic determination. These genetic brain maps reveal heritable aspects of white matter integrity and should expedite the discovery of single-nucleotide polymorphisms affecting fiber connectivity and cognition.

Key words: genetics; cognition; twins; white matter; diffusion imaging; structural equations

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Received Sept. 2, 2008; revised Jan. 14, 2009; accepted Jan. 15, 2009.

Correspondence should be addressed to Dr. Paul M. Thompson, Laboratory of Neuro Imaging, Department of Neurology, University of California, Los Angeles, School of Medicine, 635 Charles E. Young Drive South, Suite 225E, Los Angeles, CA 90095-7334. Email: thompson{at}loni.ucla.edu

This article has been cited by other articles:

				M. P. van den Heuvel, C. J. Stam, R. S. Kahn, and H. E. Hulshoff Pol Efficiency of Functional Brain Networks and Intellectual Performance J. Neurosci., June 10, 2009; 29(23): 7619 - 7624. [Abstract] [Full Text] [PDF]

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