title: Multidimensional heritability analysis of neuroanatomical shape.
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, behaviour 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.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts 02129, USA.|Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02138, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Ge
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts 02129, USA.|Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Reuter
authors.affiliation: Centre for Functional MRI of the Brain (FMRIB), University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Anderson M
authors.identifier: 0000-0002-4169-9781
authors.initials: AM
authors.lastname: Winkler
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts 02129, USA.|Department of Psychology, Yale University, New Haven, Connecticut 06520, USA.|Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Avram J
authors.initials: AJ
authors.lastname: Holmes
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02138, USA.
authors.forename: Phil H
authors.initials: PH
authors.lastname: Lee
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: Lee S
authors.identifier: 0000-0001-9393-8361
authors.initials: LS
authors.lastname: Tirrell
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Roffman
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts 02129, USA.|Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA.|Department of Psychology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Buckner
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02138, USA.
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts 02129, USA.|Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Mert R
authors.initials: MR
authors.lastname: Sabuncu
mesh_terms: D000465:Algorithms; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D063132:Connectome; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008953:Models, Anatomic; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D014427:Twins / Q000235:genetics*