Cortical Thickness Is Influenced by Regionally Specific Genetic Factors

Lars M. Rimol, Matthew S. Panizzon, Christine Fennema-Notestine, Lisa T. Eyler, Bruce Fischl, Carol E. Franz, Donald J. Hagler, Michael J. Lyons, Michael C. Neale, Jennifer Pacheco, Michele E. Perry, J. Eric Schmitt, Michael D. Grant, Larry J. Seidman, Heidi W. Thermenos, Ming T. Tsuang, Seth A. Eisen, William S. Kremen, Anders M. Dale

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

Background: Although global brain structure is highly heritable, there is still variability in the magnitude of genetic influences on the size of specific regions. Yet, little is known about the patterning of those genetic influences, i.e., whether the same genes influence structure throughout the brain or whether there are regionally specific sets of genes. Methods: We mapped the heritability of cortical thickness throughout the brain using three-dimensional structural magnetic resonance imaging in 404 middle-aged male twins. To assess the amount of genetic overlap between regions, we then mapped genetic correlations between three selected seed points and all other points comprising the continuous cortical surface. Results: There was considerable regional variability in the magnitude of genetic influences on cortical thickness. The primary visual (V1) seed point had strong genetic correlations with posterior sensory and motor areas. The anterior temporal seed point had strong genetic correlations with anterior frontal regions but not with V1. The middle frontal seed point had strong genetic correlations with inferior parietal regions. Conclusions: These results provide strong evidence of regionally specific patterns rather than a single, global genetic factor. The patterns are largely consistent with a division between primary and association cortex, as well as broadly defined patterns of brain gene expression, neuroanatomical connectivity, and brain maturation trajectories, but no single explanation appears to be sufficient. The patterns do not conform to traditionally defined brain structure boundaries. This approach can serve as a step toward identifying novel phenotypes for genetic association studies of psychiatric disorders and normal and pathological cognitive aging.

Original languageEnglish
Pages (from-to)493-499
Number of pages7
JournalBiological Psychiatry
Volume67
Issue number5
DOIs
StatePublished - Mar 1 2010

Keywords

  • Cortical thickness
  • MRI
  • endophenotypes
  • genetic correlation
  • heritability
  • imaging genetics
  • twins

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    Rimol, L. M., Panizzon, M. S., Fennema-Notestine, C., Eyler, L. T., Fischl, B., Franz, C. E., Hagler, D. J., Lyons, M. J., Neale, M. C., Pacheco, J., Perry, M. E., Schmitt, J. E., Grant, M. D., Seidman, L. J., Thermenos, H. W., Tsuang, M. T., Eisen, S. A., Kremen, W. S., & Dale, A. M. (2010). Cortical Thickness Is Influenced by Regionally Specific Genetic Factors. Biological Psychiatry, 67(5), 493-499. https://doi.org/10.1016/j.biopsych.2009.09.032