1Hum. Mol. Genet. 2011 Oct 20: 4076-81
TitleCommon variants at VRK2 and TCF4 conferring risk of schizophrenia.
AbstractCommon sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10 260 cases and 23 500 controls). In addition to previously reported alleles in the major histocompatibility complex region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) [odds ratio (OR) = 1.09, P = 1.9 10(-9)] and rs4309482[A], between coiled-coiled domain containing 68 (CCDC68) and TCF4, about 400 kb from the previously described risk allele, but not accounted for by its association (OR = 1.09, P = 7.8 10(-9)).
SCZ Keywordsschizophrenia
2Neurochem. Int. 2013 May 62: 870-2
TitleExpression and differential response to haloperidol treatment of Cyclon/CCDC86 mRNA in schizophrenia patients.
AbstractA gene known as Cyclon (cytokine-induced protein with coiled-coil domain) or CCDC86 (coiled-coil domain-containing protein 86) is known for its expression in leukocytes in mice, where it regulates the immune response. We investigated whether Cyclon/CCDC68 is expressed in leukocytes of schizophrenia patients and whether it might be used as a biological marker for the disease endophenotype segregation. We examined the level of mRNA of Cyclon/CCDC68 in white blood cells obtained from schizophrenia patients in relapse and remission as well as in healthy controls. The mRNA of Cyclon/CCDC68 was expressed by white blood cells of both schizophrenia patients and healthy controls. There was a dichotomous change in the levels of Cyclon/CCDC68 of relapsed patients before and after treatment. High Cyclon/CCDC68 levels were associated with a recent disease and presence of psychotic symptoms, while low levels were associated with a long duration of the disease and an absence of psychotic symptoms. These data indicate that Cyclon/CCDC68 levels correlate with the clinical presentation of relapsed schizophrenia. Cyclon/CCDC68 might be involved in the immune system disturbances observed in schizophrenia.
SCZ Keywordsschizophrenia
3Behav Brain Funct 2013 -1 9: 40
TitleThe impact of the genome-wide supported variant in the cyclin M2 gene on gray matter morphology in schizophrenia.
AbstractGenome-wide significant associations of schizophrenia with eight SNPs in the CNNM2, MIR137, PCGEM1, TRIM26, CSMD1, MMP16, NT5C2 and CCDC68 genes have been identified in a recent mega-analysis of genome-wide association studies. To date, the role of these SNPs on gray matter (GM) volumes remains unclear.
After performing quality control for minor-allele frequency?>?5% using a JPT HapMap sample and our sample, a genotyping call rate?>?95% and Hardy-Weinberg equilibrium testing (p?>?0.01), five of eight SNPs were eligible for analysis. We used a comprehensive voxel-based morphometry (VBM) technique to investigate the effects of these five SNPs on GM volumes between major-allele homozygotes and minor-allele carriers in Japanese patients with schizophrenia (n?=?173) and healthy subjects (n?=?449).
The rs7914558 risk variant at CNNM2 was associated with voxel-based GM volumes in the bilateral inferior frontal gyri (right T?=?4.96, p?=?0.0088, left T?=?4.66, p?=?0.031). These peak voxels, which were affected by the variant, existed in the orbital region of the inferior frontal gyri. Individuals with the risk G/G genotype of rs7914558 had smaller GM volumes in the bilateral inferior frontal gyri than carriers of the non-risk A-allele. Although several effects of the genotype and the genotype-diagnosis interaction of other SNPs on GM volumes were observed in the exploratory VBM analyses, these effects did not remain after the FWE-correction for multiple tests (p?>?0.05).
Our findings suggest that the genetic variant in the CNNM2 gene could be implicated in the pathogenesis of schizophrenia through the GM volumetric vulnerability of the orbital regions in the inferior frontal gyri.
SCZ Keywordsschizophrenia