Title :
Hierarchical clustering of the genetic connectivity matrix reveals the network topology of gene action on brain microstructure: An N=531 twin study
Author :
Chiang, Ming-Chang ; Barysheva, Marina ; McMahon, Katie L. ; De Zubicaray, Greig I. ; Johnson, Kori ; Martin, Nicholas G. ; Toga, Arthur W. ; Wright, Margaret J. ; Thompson, Paul M.
Author_Institution :
Dept. of Neurology, Lab. of Neuro Imaging, Los Angeles, CA, USA
fDate :
March 30 2011-April 2 2011
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.
Keywords :
biological NMR; biological techniques; brain; correlation methods; genetics; network topology; neurophysiology; DTI; brain microstructure; common genetic influences; diffusion tensor images; fractional anisotropy; gene action network topology; genetic connectivity matrix; genetic correlation analysis; genome wide association; hierarchical clustering; homogeneous genetic determinants; magnetic flux density 4 T; scale free topology; single nucleotide polymorphisms; white matter integrity; young adult twins; Bioinformatics; Correlation; Diffusion tensor imaging; Genomics; Network topology; diffusion tensor imaging; genome-wide association; hierarchical clustering; scale-free topology; twins;
Conference_Titel :
Biomedical Imaging: From Nano to Macro, 2011 IEEE International Symposium on
Conference_Location :
Chicago, IL
Print_ISBN :
978-1-4244-4127-3
Electronic_ISBN :
1945-7928
DOI :
10.1109/ISBI.2011.5872533