Genetics of brain structure: Contributions from the vietnam era twin study of aging

Authors

  • William S. Kremen,

    Corresponding author
    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
    2. Twin Research Laboratory, Center for Behavioral Genomics, University of California, San Diego, La Jolla, California
    3. Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, California
    • Correspondence to:

      William S. Kremen, Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093.

      E-mail: wkremen@ucsd.edu

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  • Christine Fennema-Notestine,

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
    2. Department of Radiology, University of California, San Diego, La Jolla, California
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  • Lisa T. Eyler,

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
    2. Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System, La Jolla, California
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  • Matthew S. Panizzon,

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
    2. Twin Research Laboratory, Center for Behavioral Genomics, University of California, San Diego, La Jolla, California
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  • Chi-Hua Chen,

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
    2. Twin Research Laboratory, Center for Behavioral Genomics, University of California, San Diego, La Jolla, California
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  • Carol E. Franz,

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
    2. Twin Research Laboratory, Center for Behavioral Genomics, University of California, San Diego, La Jolla, California
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  • Michael J. Lyons,

    1. Department of Psychology, Boston University, Boston, Massachusetts
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  • Wesley K. Thompson,

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
    2. Twin Research Laboratory, Center for Behavioral Genomics, University of California, San Diego, La Jolla, California
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  • Anders M. Dale

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
    2. Department of Radiology, University of California, San Diego, La Jolla, California
    3. Department of Neurosciences, University of California, San Diego, La Jolla, California
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  • Conflict of interest: All other authors have no conflicts of interest.

Abstract

Understanding the genetics of neuropsychiatric disorders requires an understanding of the genetics of brain structure and function. The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study focused on cognitive and brain aging. Here, we describe basic science work carried out within the VETSA MRI study that provides meaningful contributions toward the study of neuropsychiatric disorders. VETSA produced the first comprehensive assessment of the heritability of cortical and subcortical brain structure sizes, all within the same individuals. We showed that neocortical thickness and surface area are largely genetically distinct. With continuous neocortical thickness maps, we demonstrated regional specificity of genetic influences, and that genetic factors did not conform to traditional regions of interest (ROIs). However, there was some evidence for different genetic factors accounting for different types of cortex, and for genetic relationships across cortical regions corresponding to anatomical and functional connectivity and brain maturation patterns. With continuous neocortical surface area maps, we confirmed the anterior–posterior gradient of genetic influences on cortical area patterning demonstrated in animal models. Finally, we used twin methods to create the first map of cortical ROIs based entirely on genetically informative data. We conclude that these genetically based cortical phenotypes may be more appropriate for genetic studies than traditional ROIs based on structure or function. Our results also suggest that cortical volume—the product of thickness and surface area—is a problematic phenotype for genetic studies because two independent sets of genes may be obscured. Examples supporting the validity of these conclusions are provided. © 2013 Wiley Periodicals, Inc.

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