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Comment on Study | View All Comments on Study |
Reference | McAuley, E. Z., 2012 PMID: 22693595 |
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Citation | McAuley, E. Z., A. Scimone, et al. (2012). "Identification of Sialyltransferase 8B as a Generalized Susceptibility Gene for Psychotic and Mood Disorders on Chromosome 15q25-26." PLoS One 7(5): e38172. |
Disease Type | Bipolar Disorder & Schizophrenia |
Study Design | case-control |
Study Type | Candidate-gene association study |
Sample Size | 219 cases and 166 controls in bipolar disorder case control cohort, 310 cases and 128 controls in the Schizophrenia cohort |
SNP/Region/Marker Size | 349 SNPs |
Predominant Ethnicity | Caucasian |
Population | Australian and American |
Gender | 50% were female of Australian Bipolar disorder cohort, 85 men and 43 women cases in the Australian Schizophrenia cohort |
Age Group | adults : average age of cases=46.7 (SD=15.3), average age of controls=60.3 (SD=13.5) for bipolar disorder case control cohort |
Sample Diagnosis | Research Diagnostic Criteria (RDC) for Australian Bipolar disorder cohort, DSM-III-R for Australian Schizophrenia cohort, DSM-IV or ICD-10 for NIMH bipolar disorder and schizophrenia cohorts |
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Sample Status | Australian Bipolar disorder cohort: The Australian bipolar disorder case-control cohort was mostly selected from families previously used for linkage analysis and was recruited through the Mood Disorders Unit and Black Dog Institute, Prince of Wales Hospital/School of Psychiatry, University of New South Wales, Australia. In total, 50.5% of the sample had psychotic features, 70% had a family history of bipolar disorder, and 87% had a family history of bipolar disorder or depression. Bipolar I disorder (BPI: n=158), Bipolar II disorder (BPII: n=41), Schizoaffective Disorder-Manic type (SZ/MA: n=10), Major Depressive Disorder (MDD: n=10). Australian Schizophrenia cohort: Samples were selected from a larger cohort (n=310), initially recruited for the Australian national prevalence study of psychosis, for which diagnoses were assigned using the Diagnostic Interview for Psychosis. NIMH bipolar disorder and schizophrenia cohorts: Genome wide association study data was downloaded from the Genetic Association Information Network (GAIN) through the US based National Institutes of Health. |
Replication Size | 1034 controls and 1021 patients with bipolar disorder, 1378 controls and 1172 cases with schizophrenia from NIMH |
Technique | genotyping |
Statistical Method | Statistical analyses were performed with PLINK v1.02 software. SNPs failing the Hardy-Weinberg exact test at a 0.001 significance threshold were removed. To devise empirical P values for SNP and haplotype association, ten thousand permutations for each SNP were performed using the -mperm option. Multimarker haplotype analysis was conducted using probabilistically inferred haplotypes for each individual, generated using a standard E-M algorithm in PLINK. Haplotype association analysis was performed using the -hap-assoc option with a sliding windows (-hap-window 3) or specified haplotype (-hap-snps) approach with standard association testing. Conditional regression-based association using the -chap option was performed on specific haplotypes of interest. |
Result Summary | By a fine mapping association study in an Australian case-control cohort (n = 385), we find that the sialyltransferase 8B (ST8SIA2) gene, coding for an enzyme that glycosylates proteins involved in neuronal plasticity which has previously shown association to both schizophrenia and autism, is associated with increased risk to bipolar spectrum disorder. Nominal single point association was observed with SNPs in ST8SIA2 (rs4586379, P = 0.0043; rs2168351, P = 0.0045), and a specific risk haplotype was identified (frequency: bipolar vs controls = 0.41 vs 0.31; chi(2) = 6.46, P = 0.011, OR = 1.47). Over-representation of the specific risk haplotype was also observed in an Australian schizophrenia case-control cohort (n = 256) (chi(2) = 8.41, P = 0.004, OR = 1.82). Using GWAS data from the NIMH bipolar disorder (n = 2055) and NIMH schizophrenia (n = 2550) cohorts, the equivalent haplotype was significantly over-represented in bipolar disorder (chi(2) = 5.91, P = 0.015, OR = 1.29), with the same direction of effect in schizophrenia, albeit non-significant (chi(2) = 2.3, P = 0.129, OR = 1.09). We demonstrate marked down-regulation of ST8SIA2 gene expression across human brain development and show a significant haplotypexdiagnosis effect on ST8SIA2 mRNA levels in adult cortex (ANOVA: F(1,87) = 6.031, P = 0.016). These findings suggest that variation the ST8SIA2 gene is associated with increased risk to mental illness, acting to restrict neuronal plasticity and disrupt early neuronal network formation, rendering the developing and adult brain more vulnerable to secondary genetic or environmental insults. |
SNP | Related Gene(s) | Allele Change | Risk Allele | Statistical Values | Author Comments | Result Category |
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rs11637898 | ST8SIA2 | A/G | P-value = 0.048, Empirical P-value = 0.064, OR (95% CI)=0.75 (0.56-0.99) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. More... | Positive | |
rs11074070 | ST8SIA2 ENO1P2 | C/A | P-value = 0.036, Empirical P-value = 0.04, OR (95% CI)=0.73 (0.55-0.98) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | |
rs13380006 | ST8SIA2 C15orf32 | A/G | P-value = 0.034, Empirical P-value = 0.042, OR (95% CI)=1.41 (0.97-1.82) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | |
rs12441404 | ST8SIA2 C15orf32 | A/G | P-value = 0.034, Empirical P-value = 0.042, OR (95% CI)=1.41 (0.97-1.82) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | |
rs2035645 | ST8SIA2 | A/C | P-value = 0.042, Empirical P-value = 0.06, OR (95% CI)=1.36 (1.00-1.78) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. More... | Positive | |
rs1455773 | ST8SIA2 C15orf32 | A/G | P-value = 0.026, Empirical P-value = 0.031, OR (95% CI)=1.44 (0.99-1.86) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | |
rs2280468 | ACAN | A/G | P-value = 0.031, Empirical P-value = 0.03, OR (95% CI)=0.70 (0.51-0.96) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | |
rs2168351 | ST8SIA2 | G/A | P-value = 0.005, Empirical P-value = 0.007, OR (95% CI)=0.65 (0.49-0.89) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | |
rs3858917 | ST8SIA2 | C/A | P-value = 0.046, Empirical P-value = 0.055, OR (95% CI)=0.74 (0.56-0.99) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. More... | Positive | |
rs3784735 | ST8SIA2 | C/A | P-value = 0.032, Empirical P-value = 0.034, OR (95% CI)=0.73 (0.54-0.97) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | |
rs4777760 | RGMA | A/G | P-value = 0.042, Empirical P-value = 0.045, OR (95% CI)=0.74 (0.58-1.03) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | |
rs4586379 | ST8SIA2 | G/A | P-value = 0.004, Empirical P-value = 0.006, OR (95% CI)=0.61 (0.43-0.85) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | |
rs6496898 | SLCO3A1 | G/A | P-value = 0.033, Empirical P-value = 0.035, OR (95% CI)=1.43 (1.04-1.99) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | |
rs4777974 | ST8SIA2 | G/A | P-value = 0.041, Empirical P-value = 0.05, OR (95% CI)=1.36 (1.00-1.79) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. More... | Positive | |
rs7174649 | A/G | P-value = 0.026, Empirical P-value = 0.035, OR (95% CI)=0.63 (0.42-0.94) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | ||
rs7169541 | G/C | P-value = 0.045, Empirical P-value = 0.045, OR (95% CI)=0.74 (0.55-0.99) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | ||
rs871167 | SLCO3A1 | A/G | P-value = 0.034, Empirical P-value = 0.046, OR (95% CI)=1.39 (1.06-1.93) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive | |
rs7175812 | SLCO3A1 | G/A | P-value = 0.036, Empirical P-value = 0.035, OR (95% CI)=1.53 (1.07-2.38) in the Australian bipolar disorder cohort | Nominally significant association (P < 0.05) was found with ...... Nominally significant association (P < 0.05) was found with 18 SNPs. Association with 14 of these SNPs held true when empirical P values were obtained through 10, 000 replicate permutations. More... | Positive |
Markers | Haplotype | Related Gene(s)/Region(s) | Statistical Values | Author Comments | Result Category |
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rs4586379 - rs8025225 - rs11074066 - rs11074067 - rs2035645 | T-T-A-G-T | ST8SIA2 | P-value = 0.015, X<sup>2</sup>=5.91, OR (95% CI)=1.29 (1.03-1.33) in NIMH BP | The most common haplotype (TTAGT, equivalent to the risk hap...... The most common haplotype (TTAGT, equivalent to the risk haplotype identified in the Australian cohort) was significantly over represented in the NIMH bipolar disorder cases compared to controls. More... | Positive |
rs4586379 - rs2035645 - rs4777974 - rs11637898 - rs11074070 - rs3784735 | G-C-A-A-C-C | ST8SIA2 | P-value = 0.015, X<sup>2</sup>=5.97, OR (95% CI)=0.5857 (0.38-0.90) in Aus BP | GCAACC representing the third most common haplotype had a hi...... GCAACC representing the third most common haplotype had a higher frequency in controls than in cases, constituted a putative protective haplotype. More... | Positive |
rs4586379 - rs2035645 - rs4777974 - rs11637898 - rs11074070 - rs3784735 | A-A-G-G-A-A | ST8SIA2 | P-value = 0.011, X<sup>2</sup>=6.46, OR (95% CI)=1.473 (1.09-1.99) in Aus BP | Global significant association across a 6 SNP haplotype span...... Global significant association across a 6 SNP haplotype spanning 54 kb, starting 16 kb upstream of ST8SIA2 through to the middle of intron 2, was found with SNPs rs4586379, rs2035645, rs4777974, rs11637898, rs11074070 and rs3784735. The most common haplotype AAGGAA, had a higher frequency in cases than in controls constituted a putative bipolar risk haplotype. More... | Positive |
rs4586379 - rs8025225 - rs11074066 - rs11074067 - rs2035645 | C-C-C-C-G | ST8SIA2 | P-value = 0.09, X<sup>2</sup>=2.83, OR (95% CI)=0.87 (0.73-1.02) in NIMH BP | No significant association was reported in this study. No significant association was reported in this study. | Negative |
Gene | Statistical Values/Author Comments | Result Category |
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ST8SIA2 | These findings suggest that variation the ST8SIA2 gene is associated with increased risk to mental i...... These findings suggest that variation the ST8SIA2 gene is associated with increased risk to mental illness, acting to restrict neuronal plasticity and disrupt early neuronal network formation, rendering the developing and adult brain more vulnerable to secondary genetic or environmental insults. More... | Positive |
C15orf32 | Nominally significant association (P < 0.05) was found with 3 SNPs with BD. Nominally significant association (P < 0.05) was found with 3 SNPs with BD. | Positive |
ACAN | Nominally significant association (P < 0.05) was found with 1 SNP with BD. Nominally significant association (P < 0.05) was found with 1 SNP with BD. | Positive |
RGMA | Nominally significant association (P < 0.05) was found with 1 SNP with BD. Nominally significant association (P < 0.05) was found with 1 SNP with BD. | Positive |
SLCO3A1 | Nominally significant association (P < 0.05) was found with 3 SNPs with BD. Nominally significant association (P < 0.05) was found with 3 SNPs with BD. | Positive |
Disease | SNP | Related Gene(s) | Statistical Values | Description | Result Category |
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SZ | rs11074070 | ST8SIA2 ENO1P2 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs1455773 | ST8SIA2 C15orf32 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs13380006 | ST8SIA2 C15orf32 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs12441404 | ST8SIA2 C15orf32 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs11637898 | ST8SIA2 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs3784735 | ST8SIA2 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs2280468 | ACAN | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs2168351 | ST8SIA2 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs2035645 | ST8SIA2 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs3858917 | ST8SIA2 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs4586379 | ST8SIA2 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs4777760 | RGMA | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs4777974 | ST8SIA2 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs6496898 | SLCO3A1 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs7169541 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative | |
SZ | rs7174649 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative | |
SZ | rs7175812 | SLCO3A1 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
SZ | rs871167 | SLCO3A1 | P-value > 0.075 | Single SNP analysis did not yield significant evidence for association. | Negative |
Disease | Markers | Haplotype | Related Gene(s)/Region(s) | Statistical Values | Description | Result Category |
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SZ | rs4586379 - rs8025225 - rs11074066 - rs11074067 - rs2035645 | C-C-C-C-G | ST8SIA2 | P-value = 0.408, X<sup>2</sup>=0.68, OR (95% CI)=0.938 (0.81-1.09) in NIMH SZ | No significant association was reported in this study. | Negative |
SZ | rs4586379 - rs8025225 - rs11074066 - rs11074067 - rs2035645 | T-T-A-G-T | ST8SIA2 | P-value = 0.129, X<sup>2</sup>=2.30, OR (95% CI)=1.09 (0.97-1.23) in NIMH SZ | This haplotype also showed the same direction of effect in the NIMH cases with schizophrenia compared to controls, although it did not reach statistical significance. | Negative |
SZ | rs4586379 - rs2035645 - rs4777974 - rs11637898 - rs11074070 - rs3784735 | G-C-A-A-C-C | ST8SIA2 | P-value = 0.021, X<sup>2</sup>=5.30, OR (95% CI)=0.515 (0.29-0.92) in Aus SZ | the protective haplotype was over-represented in controls on conditional haplotype analysis | Positive |
SZ | rs4586379 - rs2035645 - rs4777974 - rs11637898 - rs11074070 - rs3784735 | A-A-G-G-A-A | ST8SIA2 | P-value = 0.004, X<sup>2</sup>=8.41, OR (95% CI)=1.82 (1.2-2.74) in Aus SZ | We found that the specific AAGGAA risk haplotype was significantly over-represented in schizophrenia cases compared to controls when a conditional analysis was performed. | Positive |
Disease | Gene | Description | Result Category |
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SZ | SLCO3A1 | No significant association was reported in this study. | Negative |
SZ | ST8SIA2 | These findings suggest that variation the ST8SIA2 gene is associated with increased risk to mental illness, acting to restrict neuronal plasticity and disrupt early neuronal network formation, rendering the developing and adult brain more vulnerable to secondary genetic or environmental insults. | Positive |
SZ | ACAN | No significant association was reported in this study. | Negative |
SZ | RGMA | No significant association was reported in this study. | Negative |
SZ | C15orf32 | No significant association was reported in this study. | Negative |
Copyright: Bioinformatics Lab, Institute of Psychology, Chinese Academy of Sciences Feedback
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Last update: March 31, 2016