| 1 | Zhonghua Liu Xing Bing Xue Za Zhi 2004 Sep 25: 787-90 |
|---|---|
| PMID | 15555361 |
| Title | [Searching for a schizophrenia susceptibility gene in the 22q11 region]. |
| Abstract | To investigate the genetic association for schizophrenia within the long arm region 1 band 1 of chromosome 22 (22q11) in a Han Chinese population. Polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis was used to detect three single nucleotide polymorphism (SNPs), rs165655 (A/G base change) and rs165815 (C/T base change) present in the ARVCF (armadillo repeat gene deletion in velocardiofacial syndrome) locus, and rs756656 (A/C base change) in the LOC128979 (expressed sequence tags, EST) locus, among 100 nuclear families composed of fathers, mothers and affected offspring with schizophrenia. Genotyping data were analyzed by linkage disequilibrium methods including haplotype relative risk (HRR) analysis, transmission disequilibrium test (TDT) and haplotype transmission analysis. The genotype frequency distributions of three SNPs were all in Hardy-Weinberg equilibrium; Both HRR and TDT analysis showed that rs165815 was associated with schizophrenia (P < 0.05), whereas the other two SNPs did not show any allelic association. The haplotype transmission analysis showed a biased transmission for the rs165655-rs165815 haplotype system and for the rs756656-rs165655-rs165815 haplotype system (P < 0.01). Either ARVCF gene itself or a nearby locus might confer susceptibility to schizophrenia in a Han Chinese population. |
| SCZ Keywords | schizophrenia |
| 2 | Schizophr. Res. 2005 Jan 72: 275-7 |
| PMID | 15560973 |
| Title | Mutation analysis of ARVCF gene on chromosome 22q11 as a candidate for a schizophrenia gene. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia |
| 3 | Biomed. Environ. Sci. 2005 Feb 18: 31-5 |
| PMID | 15861775 |
| Title | Searching for a schizophrenia susceptibility gene in the 22q11 region. |
| Abstract | To investigate a genetic association for schizophrenia within chromosome 22q11 in a Chinese Han population. The PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis was used to detect three single nucleotide polymorphisms (SNPs), rs165655 (A/G base change) and rs165815 (C/T base change) present in the ARVCF (armadillo repeat gene deletion in velocardiofacial syndrome) locus, and rs756656 (A/C base change) in the LOC128979 (expressed sequence tags, EST) locus, among 100 Chinese family trios consisting of fathers, mothers and affected offspring with schizophrenia. Genotype data were analyzed by using linkage disequilibrium (LD) methods including haplotype relative risk (HRR) analysis, transmission disequilibrium test (TDT) and haplotype transmission analysis. The genotype frequency distributions of three SNPs were all in Hardy-Weinberg equilibrium (P>0.05). Both the HRR and the TDT analysis showed that rs165815 was associated with schizophrenia (chi2=6.447, df=1, P=0.011 and chi2=6.313, df=1, P=0.012, respectively), whereas the other two SNPs did not show any allelic association. The haplotype transmission analysis showed a biased transmission for the rs165655-rs165815 haplotype system (chi2=17.224, df=3, P=0.0006) and for the rs756656-rs165655-rs165815 hapoltype system (chi2=20.965, df=7, P=0.0038). Either the ARVCF gene itself or a nearby locus may confer susceptibility to schizophrenia in a Chinese Han population. |
| SCZ Keywords | schizophrenia |
| 4 | Mol. Psychiatry 2005 Apr 10: 353-65 |
| PMID | 15340358 |
| Title | Haplotypic association spanning the 22q11.21 genes COMT and ARVCF with schizophrenia. |
| Abstract | Catechol-O-methyltransferase (COMT) has been implicated in schizophrenia by its function through its roles in monoamine neurotransmitter metabolism and its impact on prefrontal cognition, and also by its position through linkage scans and a strong cytogenetic association. Further support comes from association studies, especially family-based ones examining the COMT variant, Val(108/158)Met. We have studied eight markers spanning COMT and including portions of the two immediately adjacent genes, thioredoxin reductase 2 and armadillo repeat deleted in velocardiofacial syndrome (ARVCF), using association testing in 136 schizophrenia families. We found nominal evidence for association of illness to rs165849 (P=0.051) in ARVCF, and a stronger signal (global P=0.0019-0.0036) from three-marker haplotypes spanning the 3' portions of COMT and ARVCF, including Val(108/158)Met with Val(108/158) being the overtransmitted allele, consistent with previous studies. We also find Val(108/158)Met to be in linkage disequilibrium with the markers in ARVCF. These findings support previous association signals of schizophrenia to COMT markers, and suggest that ARVCF might contribute to this signal. ARVCF, a member of the catenin family, besides being a positional candidate, is also one due to its function, that is, its potential role in neurodevelopment, which is implicated in schizophrenia pathogenesis by several lines of evidence. |
| SCZ Keywords | schizophrenia |
| 5 | Am J Psychiatry 2008 Apr 165: 497-506 |
| PMID | 18198266 |
| Title | No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics. |
| Abstract | The authors carried out a genetic association study of 14 schizophrenia candidate genes (RGS4, DISC1, DTNBP1, STX7, TAAR6, PPP3CC, NRG1, DRD2, HTR2A, DAOA, AKT1, CHRNA7, COMT, and ARVCF). This study tested the hypothesis of association of schizophrenia with common single nucleotide polymorphisms (SNPs) in these genes using the largest sample to date that has been collected with uniform clinical methods and the most comprehensive set of SNPs in each gene. The sample included 1,870 cases (schizophrenia and schizoaffective disorder) and 2,002 screened comparison subjects (i.e. controls), all of European ancestry, with ancestral outliers excluded based on analysis of ancestry-informative markers. The authors genotyped 789 SNPs, including tags for most common SNPs in each gene, SNPs previously reported as associated, and SNPs located in functional domains of genes such as promoters, coding exons (including nonsynonymous SNPs), 3' untranslated regions, and conserved noncoding sequences. After extensive data cleaning, 648 SNPs were analyzed for association of single SNPs and of haplotypes. Neither experiment-wide nor gene-wide statistical significance was observed in the primary single-SNP analyses or in secondary analyses of haplotypes or of imputed genotypes for additional common HapMap SNPs. Results in SNPs previously reported as associated with schizophrenia were consistent with chance expectation, and four functional polymorphisms in COMT, DRD2, and HTR2A did not produce nominally significant evidence to support previous evidence for association. It is unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects cannot be ruled out. |
| SCZ Keywords | schizophrenia |
| 6 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Aug 33: 1064-9 |
| PMID | 19508883 |
| Title | ARVCF single marker and haplotypic association with schizophrenia. |
| Abstract | We present a schizophrenia association study using an extensive linkage disequilibrium (LD) mapping approach in seven candidate genes with a well established link to dopamine, including receptors (DRD2, DRD3) and genes involved in its metabolism and transport (ACE, COMT, DAT, MAO-A, MAO-B). The sample included 242 subjects diagnosed with schizophrenia and related disorders and 373 hospital-based controls. 84 tag SNPs in candidate genes were genotyped. After extensive data cleaning 70 SNPs were analyzed for association of single markers and haplotypes. One block of four SNPs (rs165849, rs2518823, rs887199 and rs2239395) in the 3' downstream region of the COMT gene which included a non-dopaminergic candidate gene, the ARVCF (Armadillo like VeloCardio Facial) gene, was associated with the risk of schizophrenia. The genetic region including the ARVCF gene in the 22q11.21 chromosome is associated with schizophrenia in a Spanish series. Our results will assist in the interpretation of the controversy generated by genetic associations of COMT and schizophrenia, which could be the result of different LD patterns between COMT markers and the 3' region of the ARVCF gene. |
| SCZ Keywords | schizophrenia |
| 7 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010 Jul 153B: 1052-9 |
| PMID | 20333729 |
| Title | A functional variant provided further evidence for the association of ARVCF with schizophrenia. |
| Abstract | In a previous linkage disequilibrium mapping study, in the 3' end of ARVCF, we identified one intronic SNP rs165849 and one haplotype block associated with schizophrenia and related disorders. The aim of the present study was to explore whether functional genetic variants in the exonic regions of ARVCF included in this haplotype block are responsible for the association observed. To achieve this objective (1) the nine exons included in this haplotype block were resequenced in a group of 242 patients with schizophrenia and related disorders (Case 1). The SNPs identified were genotyped in a hospital-based control group of 373 subjects (Control 1) and an association study was performed. (2) The SNPs showing significant association in this analysis were genotyped in a new group of 102 patients with schizophrenia and related disorders (Case 2) and in a new group of 111 healthy subjects (Control 2). Three dbSNPs (rs35219372, rs5993890, and rs165815) were identified when the nine exons of ARVCF were resequenced. rs165815 was associated with schizophrenia and related disorders (homozygote CC OR = 3.39, permutated P value = 0.02). When the groups of cases (1 and 2) and controls (1 and 2) were merged, the analysis confirmed the association observed (homozygote CC OR = 3.25 permutated P value = 0.02). Given the role of ARVCF proposed in the neurodevelopmental hypothesis, our results further support the view that chromosome 22 contains a susceptibility gene, possibly ARVCF. The functional variant rs165815, which affects a critical region of ARVCF, is a considerable source of the genetic variability associated with the risk of developing schizophrenia. |
| SCZ Keywords | schizophrenia |
| 8 | J Clin Psychiatry 2012 Mar 73: 320-6 |
| PMID | 22053977 |
| Title | ARVCF genetic influences on neurocognitive and neuroanatomical intermediate phenotypes in Chinese patients with schizophrenia. |
| Abstract | There are notable similarities between velocardiofacial syndrome and schizophrenia in terms of neurocognitive deficits and brain structural abnormalities. These similarities have supported the role of the armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) as a susceptibility gene in schizophrenia. This study investigated the relationships between haplotypes of the ARVCF gene and specific intermediate phenotypes in schizophrenia. We hypothesized that ARVCF gene haplotypes influence caudate nucleus volume, fractional anisotropy, and neurocognitive functioning in schizophrenia. Between May 2006 and November 2009, 200 Chinese participants (125 patients with DSM-IV diagnosis of schizophrenia and 75 controls) were genotyped using blood samples, and a subset of 166 participants (99 patients with DSM-IV diagnosis of schizophrenia and 67 controls) underwent structural magnetic resonance imaging, diffusion tensor imaging, and completed neuropsychological testing. The haplotype T-G-A-T-T-G-G-C-T-G-T (ARVCF-Hap1) was significantly associated with fractional anisotropy of the caudate nucleus and executive functioning in patients. Specifically, patients with more copies of ARVCF-Hap1 have lower white matter integrity in caudate nucleus (P = .0008) and greater perseverative errors (P = .00003) on the Wisconsin Card Sorting Test. A trend of lower caudate volume (P = .015) in patients with more copies of ARVCF-Hap1 was also observed. These findings are consistent with known ARVCF gene effects on neurodevelopment in terms of cellular arrangement, migration, and intracellular signaling involving the striatum and may involve interactions with other brain networks such as prefrontal cortex, and they underscore the importance of imaging-genetic studies to elucidate the genetic influences underlying intermediate phenotypes in complex neurobehavioral disorders. |
| SCZ Keywords | schizophrenia |
| 9 | Pediatrics 2014 Jun 133: e1655-63 |
| PMID | 24819575 |
| Title | Common genetic variants and risk of brain injury after preterm birth. |
| Abstract | The role of heritable factors in determining the common neurologic deficits seen after preterm birth is unknown, but the characteristic phenotype of neurocognitive, neuroanatomical, and growth abnormalities allows principled selection of candidate genes to test the hypothesis that common genetic variation modulates the risk for brain injury. We collected an MRI-linked genomic DNA library from 83 preterm infants and genotyped tag single nucleotide polymorphisms in 13 relevant candidate genes. We used tract-based spatial statistics and deformation-based morphometry to examine the risks conferred by carriage of particular alleles at tag single nucleotide polymorphisms in a restricted number of genes and related these to the preterm cerebral endophenotype. Carriage of the minor allele at rs2518824 in the armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) gene, which has been linked to neuronal migration and schizophrenia, and rs174576 in the fatty acid desaturase 2 gene, which encodes a rate-limiting enzyme for endogenous long chain polyunsaturated fatty acid synthesis and has been linked to intelligence, was associated with white matter abnormality measured in vivo using diffusion tensor imaging (P = .0009 and P = .0019, respectively). These results suggest that genetic variants modulate white matter injury after preterm birth, and known susceptibilities to neurologic status in later life may be exposed by the stress of premature exposure to the extrauterine environment. |
| SCZ Keywords | schizophrenia |