Diffusion tensor imaging data reveals GRM3 polymorphism's association with white matter integrity in schizophrenia

While the functional disconnectivity hypothesis of schizophrenia has been the subject of much study, very little is known about the contribution of individual genotypes to connectivity between brain regions in either schizophrenia patients or in healthy controls. In this study, we obtained diffusion tensor imaging (DTI) maps and genome-wide SNP data from 74 cases and 87 age- and gender-matched controls. Correlations were performed between loading coefficients obtained from fractional anisotropy (FA) values in networks of regions representing 6 maximally independent components and 134 SNPs in genes that have been found to be important in myelination and/or schizophrenia. By using independent component analysis (ICA) to analyze the FA data we move beyond single voxels (voxel based morphometry) to a source based morphometry. In doing so, we can obtain networks of FA values that covary in a similar way among subjects, and we can study the relationship between these networks and genotype. We report one SNP located in the intronic region of the metabotropic glutamate receptor 3 gene GRM3 that showed a significant correlation with connectivity in patients but not in controls (p<1.0x10-4). This SNP, rs7808623, has not been previously shown to be associated with schizophrenia, although association has been shown with several SNPs in GRM3.