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Multidimensional Heritability Analysis of Neuroanatomical Shape

Tian Ge, Martin Reuter, Anderson M. Winkler, Avram J. Holmes, Phil H. Lee, Lee S. Tirrell, Joshua L. Roffman, Randy L. Buckner, Jordan W. Smoller, Mert R. Sabuncu
doi: https://doi.org/10.1101/033407
Tian Ge
aAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School, Charlestown, MA 02129, USA
bPsychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
cStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02138, USA
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Martin Reuter
aAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School, Charlestown, MA 02129, USA
dComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Anderson M. Winkler
eCentre for Functional MRI of the Brain (FMRIB), University of Oxford, Oxford OX3 9DU, UK
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Avram J. Holmes
aAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School, Charlestown, MA 02129, USA
fDepartment of Psychology, Yale University, New Haven, CT 06520, USA
gDepartment of Psychiatry, Massachusetts General Hospital / Harvard Medical School, Boston, MA 02114, USA
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Phil H. Lee
bPsychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
cStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02138, USA
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Lee S. Tirrell
aAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School, Charlestown, MA 02129, USA
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Joshua L. Roffman
gDepartment of Psychiatry, Massachusetts General Hospital / Harvard Medical School, Boston, MA 02114, USA
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Randy L. Buckner
aAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School, Charlestown, MA 02129, USA
gDepartment of Psychiatry, Massachusetts General Hospital / Harvard Medical School, Boston, MA 02114, USA
hDepartment of Psychology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
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Jordan W. Smoller
bPsychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
cStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02138, USA
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Mert R. Sabuncu
aAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School, Charlestown, MA 02129, USA
dComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Abstract

In the dawning era of large-scale biomedical data, multidimensional phenotype vectors will play an increasing role in examining the genetic underpinnings of brain features, behavior and disease. For example, shape measurements derived from brain MRI scans are multidimensional geometric descriptions of brain structure and provide an alternate class of phenotypes that remains largely unexplored in genetic studies. Here we extend the concept of heritability to multidimensional traits, and present the first comprehensive analysis of the heritability of neuroanatomical shape measurements across an ensemble of brain structures based on genome-wide SNP and MRI data from 1,320 unrelated, young and healthy individuals. We replicate our findings in an extended twin sample from the Human Connectome Project (HCP). Our results demonstrate that neuroanatomical shape can be significantly heritable, above and beyond volume, and can serve as a complementary phenotype to study the genetic determinants and clinical relevance of brain structure.

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Posted September 20, 2016.
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Multidimensional Heritability Analysis of Neuroanatomical Shape
Tian Ge, Martin Reuter, Anderson M. Winkler, Avram J. Holmes, Phil H. Lee, Lee S. Tirrell, Joshua L. Roffman, Randy L. Buckner, Jordan W. Smoller, Mert R. Sabuncu
bioRxiv 033407; doi: https://doi.org/10.1101/033407
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Multidimensional Heritability Analysis of Neuroanatomical Shape
Tian Ge, Martin Reuter, Anderson M. Winkler, Avram J. Holmes, Phil H. Lee, Lee S. Tirrell, Joshua L. Roffman, Randy L. Buckner, Jordan W. Smoller, Mert R. Sabuncu
bioRxiv 033407; doi: https://doi.org/10.1101/033407

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