title: 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.
authors.affiliation: Clinical Neuroimaging Laboratory, Department of Psychiatry and Anatomy, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. dara.cannon@nuigalway.ie
authors.forename: D M
authors.initials: DM
authors.lastname: Cannon
authors.forename: M
authors.initials: M
authors.lastname: Walshe
authors.forename: E
authors.initials: E
authors.lastname: Dempster
authors.forename: D A
authors.initials: DA
authors.lastname: Collier
authors.forename: N
authors.initials: N
authors.lastname: Marshall
authors.forename: E
authors.initials: E
authors.lastname: Bramon
authors.forename: R M
authors.initials: RM
authors.lastname: Murray
authors.forename: C
authors.initials: C
authors.lastname: McDonald
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D001931:Brain Mapping / Q000379:methods; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000235:genetics*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D020890:Neuregulin-1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: C571326:MOG protein, human; D063308:Myelin-Oligodendrocyte Glycoprotein; C094131:NRG1 protein, human; D020890:Neuregulin-1; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571337:CNP protein, human