Twin Research and Human Genetics

Articles

A Comparison of Heritability Maps of Cortical Surface Area and Thickness and the Influence of Adjustment for Whole Brain Measures: A Magnetic Resonance Imaging Twin Study

Lisa T. Eylera1a2 c1, Chi-Hua Chena1a3, Matthew S. Panizzona1a3, Christine Fennema-Notestinea1a4, Michael C. Nealea5, Amy Jaka6a1, Terry L. Jernigana1a7, Bruce Fischla8, Carol E. Franza1a3, Michael J. Lyonsa9, Michael Granta9, Elizabeth Prom-Wormleya5, Larry J. Seidmana10, Ming T. Tsuanga1a3a11a12, Mark Joseph A. Fiecasa4, Anders M. Dalea4a13 and William S. Kremena1a3a12

a1 Department of Psychiatry, University of California San Diego, La Jolla, CA, USA

a2 Mental Illness Research, Education, & Clinical Center, VA San Diego Healthcare System, San Diego, CA, USA

a3 Center for Behavioral Genomics, University of California San Diego, La Jolla, CA, USA

a4 Department of Radiology, University of California, San Diego, La Jolla, CA, USA

a5 Departments of Psychiatry and Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA

a6 Psychology Service, VA San Diego Healthcare System, San Diego, CA, USA

a7 Department of Cognitive Science, University of California San Diego, San Diego, CA, USA

a8 Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA

a9 Department of Psychology, Boston University, Boston, MA, USA

a10 Department of Psychiatry, Harvard Medical School, Boston, MA, USA

a11 Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA

a12 Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA

a13 Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA

Abstract

Understanding the genetic and environmental contributions to measures of brain structure such as surface area and cortical thickness is important for a better understanding of the nature of brain-behavior relationships and changes due to development or disease. Continuous spatial maps of genetic influences on these structural features can contribute to our understanding of regional patterns of heritability, since it remains to be seen whether genetic contributions to brain structure respect the boundaries of any traditional parcellation approaches. Using data from magnetic resonance imaging scans collected on a large sample of monozygotic and dizygotic twins in the Vietnam Era Twin Study of Aging, we created maps of the heritability of areal expansion (a vertex-based area measure) and cortical thickness and examined the degree to which these maps were affected by adjustment for total surface area and mean cortical thickness. We also compared the approach of estimating regional heritability based on the average heritability of vertices within the region to the more traditional region-of-interest (ROI)-based approach. The results suggested high heritability across the cortex for areal expansion and, to a slightly lesser degree, for cortical thickness. There was a great deal of genetic overlap between global and regional measures for surface area, so maps of region-specific genetic influences on surface area revealed more modest heritabilities. There was greater inter-regional variability in heritabilities when calculated using the traditional ROI-based approach compared to summarizing vertex-by-vertex heritabilities within regions. Discrepancies between the approaches were greatest in small regions and tended to be larger for surface area than for cortical thickness measures. Implications regarding brain phenotypes for future genetic association studies are discussed.

(Received November 02 2011)

(Accepted January 30 2012)

Keywords:

  • surface area;
  • cortical thickness;
  • region of interest;
  • heritability maps

Correspondence:

c1 address for correspondence: Lisa T. Eyler, 9500 Gilman Drive, Mail Code 9151B, La Jolla, CA 92093, USA. E-mail: lteyler@ucsd.edu

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