Table 1.
Summary of Post-mortem Studies of Wnt-related Molecules in Schizophrenia
| Study | Investigated Association Between | Subjects | Results |
|---|---|---|---|
| J. Yang et al., 2003 [185] | rs2241802, rs2323019, rs352203 SNPs of FZD3 gene and schizophrenia | 246 Chinese Han family trios | Positive association between FZD3 locus and schizophrenia |
| Katsu et al., 2003 [187] | rs3757888, rs960914, rs2241802 SNPs of FZD3 gene and schizophrenia | Japanese population; 200 unrelated schizophrenia patients and 218 healthy controls | Positive association between rs960914 and schizophrenia |
| Emamian et al., 2004 [203] | SNPs SNP5: rs2494732, SNP4: rs1130233A, SNP3: rs3730358, SNP2: rs1130214, SNP1: rs3803300 of AKT1 gene and schizophrenia | 210 proband-parent triads and 58 extended families, containing a total of 335 individuals affected with schizophrenia or schizoaffective disorder | One three-SNP haplotype (SNP2/3/4, TCG) is associated with schizophrenia |
| Ide et al., 2004 [189] | rs2241802, rs2323019, rs352203, rs352210, rs960914 SNPs of the FZD3 gene and schizophrenia | Japanese population; 212 schizophrenia families[family samples]; 540 unrelated schizophrenia patients [case-control samples] | No association |
| Scassellati et al., 2004 [248] | Two common SNPs at position -1727 A/T and -50 C/T and a (CAA)(n) repeat polymorphism localized in intron 1 of the GSK3β gene | 147 schizophrenia patients and 212 healthy controls | No association with schizophrenia but the (CAA)(3)/(CAA)(5) heterozygotes are more often represented in the subtype of paranoid schizophrenic patients |
| Wei and Hemmings, 2004 [190] | rs2241802, rs2323019, rs352203 SNPs of FZD3 gene and schizophrenia | British population; 120 family trios (fathers, mothers and schizophrenic offspring) | No association |
| Zhang et al., 2004 [186] | 2241802, rs2323019, rs352203, rs880481 SNPs of FZD3 gene and schizophrenia | Chinese Han Population; 236 schizophrenia patients | Positive association between rs2323019 and rs880481 and schizophrenia |
| Cui et al., 2005 [263] | rs2229992, rs42427, rs465899 SNPs at the exon region of APC gene and schizophrenia; measurement of APC mRNA in leukocytes of patients with schizophrenia | Chinese population; six schizophrenic patients and six healthy controls. 59 patients with schizophrenia and schizophrenia-like disorders and 30 healthy controls. 163 parent- offspring trios | Presence of association; an increase mRNA is found in leukocytes. |
| Hashimoto et al., 2005 [191] | rs960914, rs2241802, rs2323019, rs352203 SNPs of FZD3 gene and major psychosis | Japanese population; 427 patients with schizophrenia, 91 with bipolar disorder, 396 with major depression and 473 healthy controls | No association |
| Ikeda et al., 2005 [249] | rs4388007, rs2037547 SNPs of the GSK3β gene and schizophrenia, age-at-onset and subtypes of schizophrenia | Japanese population; 381 schizophrenic patients and 352 controls | No association |
| Lee et al., 2006 [250] | SNPs at position -1727 A/T, -50 C/T of GSK3β polymorphisms and schizophrenia | Korean population; 138 schizophrenia patients, 120 bipolar patients and 350 controls | No association |
| Szczepankiewicz et al., 2006 [251] | -50 T/C polymorphism of GSK3β gene and schizophrenia and bipolar disorder | 402 schizophrenia patients, 416 bipolar patients and 408 controls | No association with schizophrenia |
| Pinheiro et al., 2007 [219] | rs2494732, rs2498799, rs3730358, rs1130241, rs3803300 AKT1 SNPs and neurocognitive domains in schizophrenia | 641 individuals with schizophrenia | No association |
| Xu et al., 2007 [214] | Five SNPs (rs3803300, rs1130214, rs3730358, rs2498799, rs2494732) of the AKT1 gene and schizophrenia | Chinese population; 384 patients with schizophrenia vs. 384 healthy controls | G allele of rs3803300 SNP is associated; haplotype A-G-C-G-A constructed by 5 SNPs is associated |
| Kishimoto et al., 2008 [195] | rs3757888, rs960914, rs2241802, rs2323019, rs352203, rs880481 SNPs of the FZD3 gene and methamphetamine psychosis | Japanese population; 188 patients with methamphetamine psychosis and 240 controls. | Haplotype frequency of G-A-T-G and A-G-C-A of rs2241802, rs2323019 and rs352203 SNP were significantly lower in patients with methamphetamine psychosis than in controls |
| J. Meng et al., 2008 [252] | rs334563, rs12630592, rs4688054, rs10934503, rs2319398 and rs4624596 SNPs of GSK3β gene and schizophrenia (case-control study) | Chinese population; 329 schizophrenia patients and 288 healthy controls | No association |
| Proitsi et al., 2008 [300] | 50 SNPs in 28 Wnt signaling genes and schizophrenia | 307 family-trios of Chinese origin; case-control samples of over 500 schizophrenia cases and 500 controls from Hong Kong | rs2073665 SNPs in DKK4 gene is associated with schizophrenia |
| Souza et al., 2008 [254] | rs7624540, rs4072520, and rs6779828 SNPs of GSK-3β and schizophrenia | Caucasian population; 150 schizophrenia patients, 85 small nuclear families and 185 healthy controls | Positive association |
| Tan et al., 2008 [220] | rs2494732, rs1130233A, rs3730358, rs1130214, rs3803300, SNPs of AKT1 gene and cognition in healthy subjects; effects of rs1130233 SNP of AKT1 gene on AKT1 protein in peripheral lymphoblasts of healthy subjects; association between rs1130233 SNP of AKT1 gene and prefrontal function and cortical DA function using fMRI in healthy subjects; association between rs1130233 SNP of AKT1 gene and brain structure using MRI Family-based and a non-independent case-control association study: association between rs2494732, rs1130233A, rs3730358, rs1130214, rs3803300, SNPs of AKT1 gene and schizophrenia | European population 319 individuals for cognitive tests 32 healthy controls for AKT1 protein expression in lymphoblasts 46 and 68 healthy subjects for fMRI 171 individuals for structural brain MRI 358 unrelated probands and 370 unrelated healthy controls for family-based and a non-independent case-control association study | Positive association is found between rs 1130233 SNP and brain volume reductions in the caudate bilaterally and right prefrontal cortex in patients with schizophrenia rs1130233 is associated with reduced performance on cognitive functions, with reduced AKT1 protein levels, with increased prefrontal activation (inefficient activation) rs1130233 is associated with relatively reduced gray-matter volumes in the bilateral caudate and right prefrontal cortex rs1130233 is associated with increased risk for schizophrenia in the case control dataset but not in the non-independent family-based association study |
| Thiselton et al., 2008 [205] | rs1130214, rs2494732, rs2498799, rs3730358 rs2494746, rs3803304, rs2498802, rs2498804 SNPs of the AKT1 gene and schizophrenia | Irish population; 265 high-density schizophrenia families with 1408 individuals available for genotyping. | No association |
| Gregorio et al., 2009 [194] | G/C (intron 2) of Wnt7A gene, SNP1 rs3730358, SNP2 rs2498784, of AKT1 gene and MRI morphological alterations observed in 25 patients with schizophrenia; associations between impaired left/right gyrification index and protocadherin 12 gene SNP rs164515, and between ventricular enlargement and reelin gene SNP rs362691 | Twenty-five schizophrenic patients | No association |
| Stefansson et al., 2009 [281] | rs9960767 SNP of TCF4 gene and sensorimotor gating in schizophrenia | European population; 2663 patients with schizophrenia and 13498 controls | Positive association between rs9960767 SNP and schizophrenia |
| Aleksic et al., 2010 [298] | rs713526 SNP in the promoter region of KREMEN1 and schizophrenia | Japanese population; 1624 patients with schizophrenia and 1621 healthy volunteers | Presence of association |
| Benedetti et al., 2010 [168] | rs334558 SNP of GSK3β gene and grey matter volumes (voxel-based morphometry) in schizophrenic patients | 57 schizophrenia patients | Carriers of C allele variant showed higher brain volumes in an area comprising posterior regions of right middle and superior temporal gyri |
| H.J. Kim et al., 2010 [72] | rs2024233, rs1051751, rs733154, rs3779548, rs17132543, rs6948009, rs4730775, rs39315 SNPs of the Wnt2 gene and schizophrenia | Korean population; 288 patients with schizophrenia and 305 healthy controls | Weak positive association between rs4730775 and schizophrenia only, none for other SNPs |
| C. Kang et al., 2011 [193] | FZD3 SNPs rs2241802, rs2323019, rs352203, rs880481, and rs3757888 and schizophrenia | 81 Va Chinese patients with schizophrenia vs. 210 healthy controls | Haplotype analyses showed significant differences between patients and controls at rs2241802 only, after Bonferroni correction, and differences at at rs2241802-rs2323019-rs352203 haplotype |
| Lennertz et al., 2011 [284, 285] | C allele of the rs9960767 polymorphism of the TCF4 gene and verbal declarative memory (VDM) functions in schizophrenia | 401 patients with schizophrenia | Carriers of the C allele were less impaired in recognition compared to those carrying the AA genotype |
| J. Li et al., 2011 [271] | BCL-9 SNPs rs9326555, rs10494251, rs1240083, rs672607, rs688325, and rs3766512 and schizophrenia, bipolar disorder or major depressive disorder | 4187 Chinese Han patients with schizophrenia vs. 5772 healthy controls vs. 1135 patients with bipolar disorder vs. 1135 patients with major depressive disorder | Association between SNPs rs9326555, rs10494251, rs1240083, rs672607 (strongest), rs688325, and rs3766512 and schizophrenia, rs672607 and bipolar disorder, and rs672607, rs1541187, rs688325, rs10494251, rs946903 and major depressive disorder |
C=Controls; ELISA=Enzyme-linked immuno sorbent assay.