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

TY - JOUR

T1 - 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

AU - Cannon, D. M.

AU - Walshe, M.

AU - Dempster, E.

AU - Collier, D. A.

AU - Marshall, N.

AU - Bramon-Bosch, Elvira

AU - Murray, R. M.

AU - McDonald, C.

PY - 2012/10

Y1 - 2012/10

N2 - 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

AB - 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

KW - CNP

KW - HAP(ICE)

KW - MOG

KW - NRG1

KW - voxel-based morphometry

KW - white matter

KW - 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE

KW - NONFAMILIAL SCHIZOPHRENIC PROBANDS

KW - DORSOLATERAL PREFRONTAL CORTEX

KW - ANTERIOR CINGULATE CORTEX

KW - MYELINATION-RELATED GENES

KW - FAMILY-BASED ASSOCIATION

KW - BIPOLAR DISORDER

KW - GENOME SCAN

KW - OLIGODENDROGLIAL ABNORMALITIES

KW - SUSCEPTIBILITY LOCI

U2 - 10.1038/tp.2012.82

DO - 10.1038/tp.2012.82

M3 - Article

SN - 2158-3188

VL - 2

JO - Translational psychiatry

JF - Translational psychiatry

M1 - e167

ER -