Heritability of subcortical and limbic brain volume and shape in multiplex-multigenerational families with schizophrenia

David R. Roalf, Simon N. Vandekar, Laura Almasy, Kosha Ruparel, Theodore D. Satterthwaite, Mark A. Elliott, Jamie Podell, Sean Gallagher, Chad T. Jackson, Konasale Prasad, Joel Wood, Michael F. Pogue-Geile, Vishwajit L. Nimgaonkar, Ruben C. Gur, Raquel E. Gur

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Background Brain abnormalities of subcortical and limbic nuclei are common in patients with schizophrenia, and variation in these structures is considered a putative endophenotype for the disorder. Multiplex-multigenerational families with schizophrenia provide an opportunity to investigate the impact of shared genetic ancestry, but these families have not been previously examined to study structural brain abnormalities. We estimate the heritability of subcortical and hippocampal brain volumes in multiplex-multigenerational families and the heritability of subregions using advanced shape analysis.

Methods The study comprised 439 participants from two sites who underwent 3T structural magnetic resonance imaging. The participants included 190 European-Americans from 32 multiplex-multigenerational families with schizophrenia and 249 healthy comparison subjects. Subcortical and hippocampal volume and shape were measured in 14 brain structures. Heritability was estimated for volume and shape.

Results Volume and shape were heritable in families. Estimates of heritability in subcortical and limbic volumes ranged from.45 in the right hippocampus to.84 in the left putamen. The shape of these structures was heritable (range,.40-.49), and specific subregional shape estimates of heritability tended to exceed heritability estimates of volume alone.

Conclusions These results demonstrate that volume and shape of subcortical and limbic brain structures are potential endophenotypic markers in schizophrenia. The specificity obtained using shape analysis may improve selection of imaging phenotypes that better reflect the underlying neurobiology. Our findings can aid in the identification of specific genetic targets that affect brain structure and function in schizophrenia.

Original languageEnglish (US)
Pages (from-to)137-146
Number of pages10
JournalBiological Psychiatry
Issue number2
StatePublished - Jan 15 2015
Externally publishedYes


  • Endophenotypes
  • Heritability
  • Hippocampus
  • Neuroimaging-genetics
  • Schizophrenia
  • Structural MRI

ASJC Scopus subject areas

  • Biological Psychiatry


Dive into the research topics of 'Heritability of subcortical and limbic brain volume and shape in multiplex-multigenerational families with schizophrenia'. Together they form a unique fingerprint.

Cite this