Hierarchical clustering of the genetic connectivity matrix reveals the network topology of gene action on brain microstructure: An N=531 twin study

Ming Chang Chiang, Marina Barysheva, Katie L. McMahon, Greig I. De Zubicaray, Kori Johnson, Nicholas G. Martin, Arthur W. Toga, Margaret J. Wright, Paul M. Thompson

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

5 Scopus citations

Abstract

Genetic correlation (rg) analysis determines how much of the correlation between two measures is due to common genetic influences. In an analysis of 4 Tesla diffusion tensor images (DTI) from 531 healthy young adult twins and their siblings, we generalized the concept of genetic correlation to determine common genetic influences on white matter integrity, measured by fractional anisotropy (FA), at all points of the brain, yielding an NxN genetic correlation matrix rg(x,y) between FA values at all pairs of voxels in the brain. With hierarchical clustering, we identified brain regions with relatively homogeneous genetic determinants, to boost the power to identify causal single nucleotide polymorphisms (SNP). We applied genome-wide association (GWA) to assess associations between 529,497 SNPs and FA in clusters defined by hubs of the clustered genetic correlation matrix. We identified a network of genes, with a scale-free topology, that influences white matter integrity over multiple brain regions.

Original languageEnglish
Title of host publication2011 8th IEEE International Symposium on Biomedical Imaging
Subtitle of host publicationFrom Nano to Macro, ISBI'11
Pages832-835
Number of pages4
DOIs
StatePublished - 2011
Externally publishedYes
Event2011 8th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI'11 - Chicago, IL, United States
Duration: 30 Mar 20112 Apr 2011

Publication series

NameProceedings - International Symposium on Biomedical Imaging
ISSN (Print)1945-7928
ISSN (Electronic)1945-8452

Conference

Conference2011 8th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI'11
Country/TerritoryUnited States
CityChicago, IL
Period30/03/112/04/11

Keywords

  • diffusion tensor imaging
  • genome-wide association
  • hierarchical clustering
  • scale-free topology
  • twins

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