Genetic patterns of correlation among subcortical volumes in humans: Results from a magnetic resonance imaging twin study

Authors

  • Lisa T. Eyler,

    Corresponding author
    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, San Diego, California
    • 9500 Gilman Drive, Mail Code 9151B, La Jolla, California 92093
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  • Elizabeth Prom-Wormley,

    1. Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia
    2. Departments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Christine Fennema-Notestine,

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
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  • Matthew S. Panizzon,

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
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  • Michael C. Neale,

    1. Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia
    2. Departments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Terry L. Jernigan,

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
    2. Department of Cognitive Science, University of California, San Diego, La Jolla, California
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  • Bruce Fischl,

    1. Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts
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  • Carol E. Franz,

    1. Department of Psychiatry, 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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  • Allison Stevens,

    1. Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts
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  • Jennifer Pacheco,

    1. Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts
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  • Michele E. Perry,

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
    2. Department of Cognitive Science, University of California, San Diego, La Jolla, California
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  • J. Eric Schmitt,

    1. Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia
    2. Departments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Nicholas C. Spitzer,

    1. Department of Biology, University of California San Diego, La Jolla, California
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  • Larry J. Seidman,

    1. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
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  • Heidi W. Thermenos,

    1. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
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  • Ming T. Tsuang,

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
    2. Center for Behavioral Genomics, University of California San Diego, La Jolla, California
    3. Institute of Psychiatric Epidemiology and Genetics, Harvard University, Boston, Massachusetts
    4. Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, California
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  • Anders M. Dale,

    1. Department of Radiology, University of California, San Diego, La Jolla, California
    2. Department of Neurosciences, University of California, San Diego, La Jolla, California
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  • William S. Kremen

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
    2. 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, San Diego, California
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Abstract

Little is known about genetic influences on the volume of subcortical brain structures in adult humans, particularly whether there is regional specificity of genetic effects. Understanding patterns of genetic covariation among volumes of subcortical structures may provide insight into the development of individual differences that have consequences for cognitive and emotional behavior and neuropsychiatric disease liability. We measured the volume of 19 subcortical structures (including brain and ventricular regions) in 404 twins (110 monozygotic and 92 dizygotic pairs) from the Vietnam Era Twin Study of Aging and calculated the degree of genetic correlation among these volumes. We then examined the patterns of genetic correlation through hierarchical cluster analysis and by principal components analysis. We found that a model with four genetic factors best fit the data: a Basal Ganglia/Thalamus factor; a Ventricular factor; a Limbic factor; and a Nucleus Accumbens factor. Homologous regions from each hemisphere loaded on the same factors. The observed patterns of genetic correlation suggest the influence of multiple genetic influences. There is a genetic organization among structures which distinguishes between brain and cerebrospinal fluid spaces and between different subcortical regions. Further study is needed to understand this genetic patterning and whether it reflects influences on early development, functionally dependent patterns of growth or pruning, or regionally specific losses due to genes involved in aging, stress response, or disease. Hum Brain Mapp, 2011. © 2010 Wiley-Liss, Inc.

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