Elsevier

Biological Psychiatry

Volume 67, Issue 5, 1 March 2010, Pages 493-499
Biological Psychiatry

Archival Report
Cortical Thickness Is Influenced by Regionally Specific Genetic Factors

https://doi.org/10.1016/j.biopsych.2009.09.032Get rights and content

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.

Section snippets

Participants

Participants were part of the Vietnam Era Twin Study of Aging (VETSA). An overview of the VETSA project can be found elsewhere (13). A total of 1237 twins participated in wave one of this longitudinal study, and a subset underwent magnetic resonance imaging (MRI). This article is based on 474 twins who had analyzable scans to date; the twin analyses included 404 twins: 110 monozygotic (MZ) and 92 dizygotic (DZ) pairs. To date, 56% of the MRI study participants have had zygosity determined by 25

Heritability Maps of Cortical Thickness

Heritability varied substantially across the cortical surface from as low as .16 to as high as .73 (Figure 1;Figure S2 in Supplement 1 for other views). The highest heritabilities were observed bilaterally in posterior frontal and anterior medial occipital cortex and temporal pole in the left hemisphere. The lowest heritability estimates were observed in middle and inferior lateral temporal cortex (especially in the left hemisphere) and anterior prefrontal and orbitofrontal cortex (especially

Patterns of Heritability

There was substantial variability in the extent of genetic and environmental influences across brain regions, but the pattern does not lend itself to any simple interpretation in terms of cortex type or functional systems. A dissociation between primary and association cortex cannot adequately account for the findings because frontal and temporal association areas are on the opposite extremes of heritability (higher in frontal and lower in temporal), whereas primary visual and somatosensory

References (46)

  • J. Jovicich et al.

    MRI-derived measurements of human subcortical, ventricular and intracranial brain volumes: Reliability effects of scan sessions, acquisition sequences, data analyses, scanner upgrade, scanner vendors and field strengths

    Neuroimage

    (2009)
  • C. Price et al.

    Speech-specific auditory processing: Where is it?

    Trends Cogn Sci

    (2005)
  • D.C. Van Essen

    Towards a quantitative, probabilistic neuroanatomy of cerebral cortex

    Cortex

    (2004)
  • R.S. Desikan et al.

    An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest

    Neuroimage

    (2006)
  • D.D. O'Leary et al.

    Area patterning of the mammalian cortex

    Neuron

    (2007)
  • J.P. Lerch et al.

    Mapping anatomical correlations across cerebral cortex (MACACC) using cortical thickness from MRI

    Neuroimage

    (2006)
  • J.S. Peper et al.

    Genetic influences on human brain structure: A review of brain imaging studies in twins

    Hum Brain Mapp

    (2007)
  • J.E. Schmitt et al.

    Review of twin and family studies on neuroanatomic phenotypes and typical neurodevelopment

    Twin Res Hum Genet

    (2007)
  • M.C. Neale et al.

    Methodology for Genetic Studies of Twins and Families

    (1992)
  • J.E. Schmitt et al.

    Identification of genetically mediated cortical networks: A multivariate study of pediatric twins and siblings

    Cereb Cortex

    (2008)
  • P.M. Thompson et al.

    Genetic influences on brain structure

    Nat Neurosci

    (2001)
  • H.D. Rosas et al.

    Regional and progressive thinning of the cortical ribbon in Huntington's disease

    Neurology

    (2002)
  • M.S. Panizzon et al.

    Distinct genetic influences on cortical surface area and cortical thickness

    Cereb Cortex

    (2009)
  • Cited by (113)

    • Understanding the human brain: insights from comparative biology

      2022, Trends in Cognitive Sciences
      Citation Excerpt :

      Similarly, genetic correlations for relative brain region size are low in three-spined sticklebacks [89]. Finally, human genome-wide association studies and twin studies suggest that: (i) genetic variants tend to show brain region-specific volumetric effects [90], (ii) there are substantial region-specific genetic contributions to the heritability of various subcortical region volumes [91], (iii) genetic influences on cortical versus subcortical brain structures tend to be particularly distinct [92], and (iv) genetic effects on cortical thickness are largely region-specific [93]. Overall, new work suggests that neuroanatomical changes in response to selection are not highly constrained by a conserved developmental program (or pleiotropy).

    • Comparison of first-episode and multiple-episode bipolar disorder: A surface-based morphometry study

      2020, Psychiatry Research - Neuroimaging
      Citation Excerpt :

      Although cortical thickness in several regions were significantly different between groups on region wise analysis, this significance was negated after controlling for multiple comparisons. Our findings add to previous studies which investigated the abnormalities in cortical surface area, volume, and thickness in BD (Abé et al., 2016; Rimol et al., 2010). Our findings of cortical abnormalities in the rostral middle frontal gyrus (dorsolateral prefrontal cortex - DLPFC), right post central gyrus, bilateral cuneus, and left middle temporal gyrus is in tune with previous studies (Hibar et al., 2017; Robinson et al., 2009; Wessa and Linke, 2009).

    View all citing articles on Scopus

    Authors WSK and AMD contributed equally to this work.

    View full text