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Translational Psychiatry
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The association of white matter volume in psychotic disorders with genotypic variation in NRG1, MOG and CNP: a voxel-based analysis in affected individuals and their unaffected relatives

Authors: Cannon, DM; Walshe, M; Dempster, E; Collier, DA; Marshall, N; Bramon, E; Murray, RM; +1 Authors

The association of white matter volume in psychotic disorders with genotypic variation in NRG1, MOG and CNP: a voxel-based analysis in affected individuals and their unaffected relatives

Abstract

We investigated the role of variation in putative psychosis genes coding for elements of the white matter system by examining the contribution of genotypic variation in three single-nucleotide polymorphisms (SNPs) neuregulin 1 (NRG1) SNP8NRG221533, myelin oligodendrocytes glycoprotein (MOG) rs2857766 and CNP (rs2070106) and one haplotype HAP(ICE) (deCODE) to white matter volume in patients with psychotic disorder and their unaffected relatives. Structural magnetic resonance imaging and blood samples for genotyping were collected on 189 participants including patients with schizophrenia (SZ) or bipolar I disorder (BDI), unaffected first-degree relatives of these patients and healthy volunteers. The association of genotypic variation with white matter volume was assessed using voxel-based morphometry in SPM5. The NRG1 SNP and the HAP(ICE) haplotype were associated with abnormal white matter volume in the BDI group in the fornix, cingulum and parahippocampal gyrus circuit. In SZ the NRG1 SNP risk allele was associated with lower white matter volume in the uncinate fasciculus (UF), right inferior longitudinal fasciculus and the anterior limb of the internal capsule. Healthy G-homozygotes of the MOG SNP had greater white matter volume in areas of the brainstem and cerebellum; this relationship was absent in those with a psychotic disorder and the unaffected relatives groups. The CNP SNP did not contribute to white matter volume variation in the diagnostic groups studied. Variation in the genes coding for structural and protective components of myelin are implicated in abnormal white matter volume in the emotion circuitry of the cingulum, fornix, parahippocampal gyrus and UF in psychotic disorders. Translational Psychiatry (2012) 2, e167; doi:10.1038/tp.2012.82; published online 9 October 2012

Keywords

Male, 2',3'-cyclic nucleotide 3'-phosphodiesterase, Nerve Fibers, Myelinated, 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase, Image Processing, Computer-Assisted, bipolar disorder, Brain Mapping, dorsolateral prefrontal cortex, MYELINATION-RELATED GENES, oligodendroglial abnormalities, Brain, BIPOLAR DISORDER, Middle Aged, Magnetic Resonance Imaging, GENOME SCAN, anterior cingulate cortex, CNP, myelination-related genes, Original Article, Female, white matter, Adult, SUSCEPTIBILITY LOCI, Adolescent, Genotype, DORSOLATERAL PREFRONTAL CORTEX, Neuregulin-1, 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE, 610, genome scan, nonfamilial schizophrenic probands, Polymorphism, Single Nucleotide, hap(ice), 616, MOG, Humans, voxel-based morphometry, Family, Genetic Predisposition to Disease, cnp, FAMILY-BASED ASSOCIATION, Aged, NRG1, HAP(ICE), family-based association, susceptibility loci, OLIGODENDROGLIAL ABNORMALITIES, nrg1, NONFAMILIAL SCHIZOPHRENIC PROBANDS, Psychotic Disorders, ANTERIOR CINGULATE CORTEX, Myelin-Oligodendrocyte Glycoprotein, mog

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    Top 10%
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
53
Top 10%
Average
Top 10%
Green
gold