Neuroinformatics

, Volume 4, Issue 1, pp 5–19

Mapping heritability and molecular genetic associations with cortical features using probabilistic brain atlases

Methods and applications to schizophrenia
  • Tyrone D. Cannon
  • Paul M. Thompson
  • Theo G. M. van Erp
  • Matti Huttunen
  • Jouko Lonnqvist
  • Jaakko Kaprio
  • Arthur W. Toga
Original Article

DOI: 10.1385/NI:4:1:5

Cite this article as:
Cannon, T.D., Thompson, P.M., van Erp, T.G.M. et al. Neuroinform (2006) 4: 5. doi:10.1385/NI:4:1:5
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Abstract

There is an urgent need to decipher the complex nature of genotype-phenotype relationships within the multiple dimensions of brain structure and function that are compromised in neuropsychiatric syndromes such as schizophrenia. Doing so requires sophisticated methodologies to represent population variability in neural traits and to probe their heritable and molecular genetic bases. We have recently developed and applied computational algorithms to map the heritability of, as well as genetic linkage and association to, neural features encoded using brain imaging in the context of three-dimensional (3D), population-based, statistical brain atlases. One set of algorithms builds on our prior work using classical twin study methods to estimate heritability by fitting biometrical models for additive genetic, unique, and common environmental influences. Another set of algorithms performs regression-based (Haseman-Elston) identical-bydescent linkage analysis and genetic association analysis of DNA polymorphisms in relation to neural traits of interest in the same 3D population-based brain atlas format. We demonstrate these approaches using samples of healthy monozygotic (MZ) and dizygotic (DZ) twin pairs, as well as MZ and DZ twin pairs discordant for schizophrenia, but the methods can be generalized to other classes of relatives and to other diseases. The results confirm prior evidence of genetic influences on gray matter density in frontal brain regions. They also provide converging evidence that the chromosome 1q42 region is relevant to schizophrenia by demonstrating linkage and association of markers of the Transelin-Associated-Factor-X and Disrupted-In-Schizophrenia-1 genes with prefrontal cortical gray matter deficits in twins discordant for schizophrenia.

Index Entries

Brain imaging molecular genetics heritability schizophrenia neuroanatomy 

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  • Tyrone D. Cannon
    • 1
  • Paul M. Thompson
    • 2
  • Theo G. M. van Erp
    • 1
  • Matti Huttunen
    • 3
  • Jouko Lonnqvist
    • 3
  • Jaakko Kaprio
    • 3
  • Arthur W. Toga
    • 2
  1. 1.Departments of Psychology, Psychiatry and Biobehavioral SciencesUCLALos AngelesUSA
  2. 2.Department of Neurology and Laboratory of Neuro Imaging, UCLALos AngelesUSA
  3. 3.Department of Mental Health and Alcohol ResearchNational Public Health InstituteHelsinkiFinland

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