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Study Report
| Comment on Study | View All Comments on Study |
| Reference | Nyegaard, M., 2010 PMID: 19693800 |
|---|---|
| Citation | Nyegaard, M., J. E. Severinsen, et al. (2010). "Support of association between BRD1 and both schizophrenia and bipolar affective disorder." Am J Med Genet B Neuropsychiatr Genet 153B(2): 582-591. |
| Disease Type | Bipolar Disorder & Schizophrenia |
| Study Design | case-control |
| Study Type | Candidate-gene association study |
| Sample Size | 490 patients with BPD, 527 patients with SZ, and 601 control individuals for UK/DK sample; 506 bipolar patients and 510 controls for UCL sample. |
| SNP/Region/Marker Size | 11 SNPs for UK/DK sample, 7 SNPs for UCL sample |
| Predominant Ethnicity | Caucasian |
| Population | Denmark and England, English |
| Sample Diagnosis | ICD-10-DCR and DSM-IV |
|---|---|
| Technique | Genotyping in the UK/DK sample was carried out using the Sequenom MassARRAY Genotyping system. For the UCL sample, genotyping was performed at the Broad Institute ofHarvard andMIT using the Affymetrix 500Karray. |
| Statistical Method | Data quality control and association analysis were performed using the open-source toolset PLINK. Single marker association analysis was performed using the Cochran-Armitage trend test. Correction for multiple testing was performed using the method proposed by Nyholt. The degree of LD in the CEU population and in the UK/DK sample was calculated with the program HaploView. Tests for genetic homogeneity across samples were performed by applying an exact test as implemented in Arlequin. Association analysis stratified for collection site was carried out using the Cochran-Mantel-Haenszel test. |
| Result Summary | In the UK/DK sample we genotyped 11 SNPs in the BRD1 region, of which six showed association with SZ (minimal single marker P-values of 0.0014). Haplotype analysis revealed specific risk as well as protective haplotypes with a minimal P-value of 0.0027. None of the 11 SNPs showed association with BPD. However, analyzing seven BRD1 SNPs obtained from the BPD GWA study, positive associations with BPD was observed with all markers (minimal P-value of 0.0014). |
| SNP | Related Gene(s) | Allele Change | Risk Allele | Statistical Values | Author Comments | Result Category |
|---|---|---|---|---|---|---|
| rs4468 | BRD1 | T/C | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | ||
| rs3788731 | ZBED4 BRD1 | G/C | P-value = 0.0065 in UCL sample, P-value = 0.03 in WTCCC sample, P-value = 0.007 in meta-analysis result | In the UCL sample significant allelic association with BPD w...... In the UCL sample significant allelic association with BPD was observed for all seven SNPs with a minimal P-value of 0.0014. More... | Positive | |
| rs5769750 | BRD1 ZBED4 | G/A | P-value = 0.0022 in UCL sample, P-value = 0.04 in WTCCC sample, P-value = 0.006 in meta-analysis result | In the UCL sample significant allelic association with BPD w...... In the UCL sample significant allelic association with BPD was observed for all seven SNPs with a minimal P-value of 0.0014. More... | Positive | |
| rs4624 | ZBED4 | G/A | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | ||
| rs6009917 | ZBED4 | G/A | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | ||
| rs5770755 | ZBED4 | C/T | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | ||
| rs910799 | ZBED4 | G/A | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | ||
| rs138841 | BRD1 | C/A | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | ||
| rs138830 | BRD1 | G/A | P-value = 0.0035 in UCL sample, P-value = 0.036 in WTCCC sample, P-value = 0.006 in meta-analysis result | In the UCL sample significant allelic association with BPD w...... In the UCL sample significant allelic association with BPD was observed for all seven SNPs with a minimal P-value of 0.0014. More... | Positive | |
| rs138820 | BRD1 | T/C | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | ||
| rs2239848 | BRD1 | G/A | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | ||
| rs139811 | RN7SKP252 BRD1 | G/T | P-value = 0.0099 in UCL sample, P-value = 0.114 in WTCCC sample, P-value = 0.027 in meta-analysis result | In the UCL sample significant allelic association with BPD w...... In the UCL sample significant allelic association with BPD was observed for all seven SNPs with a minimal P-value of 0.0014. More... | Positive | |
| rs138887 | BRD1 | T/C | P-value = 0.0014 in UCL sample, P-value = 0.06 in WTCCC sample, P-value = 0.012 in meta-analysis result | In the UCL sample significant allelic association with BPD w...... In the UCL sample significant allelic association with BPD was observed for all seven SNPs with a minimal P-value of 0.0014. More... | Positive | |
| rs138880 | BRD1 | A/C | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | ||
| rs138864 | BRD1 | G/A | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | ||
| rs138863 | BRD1 | A/G | P-value = 0.0021 in UCL sample, P-value = 0.048 in WTCCC sample, P-value = 0.008 in meta-analysis result | In the UCL sample significant allelic association with BPD w...... In the UCL sample significant allelic association with BPD was observed for all seven SNPs with a minimal P-value of 0.0014. More... | Positive | |
| rs138855 | BRD1 | G/C | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | ||
| rs138851 | BRD1 | T/C | P-value = 0.0039 in UCL sample, P-value = 0.051 in WTCCC sample, P-value = 0.009 in meta-analysis result | In the UCL sample significant allelic association with BPD w...... In the UCL sample significant allelic association with BPD was observed for all seven SNPs with a minimal P-value of 0.0014. More... | Positive |
| Markers | Haplotype | Related Gene(s)/Region(s) | Statistical Values | Author Comments | Result Category |
|---|---|---|---|---|---|
| rs4468 rs138841 | CA | BRD1 | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | |
| rs4468 rs138841 | TC | BRD1 | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | |
| rs138841 - rs138855 - rs138864 | CGG | BRD1 | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | |
| rs138864 - rs2239848 | GG | BRD1 | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | |
| rs4468 - rs138841 - rs138855 | TCG | BRD1 | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | |
| rs138820 - rs4468 | CC | BRD1 | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | |
| rs138820 - rs4468 - rs138841 | TTC | BRD1 | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | |
| rs138841 - rs138855 | CG | BRD1 | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | |
| rs138820 - rs4468 | TT | BRD1 | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative | |
| rs138820 - rs4468 - rs138841 | CCA | BRD1 | None of the 11 Sequenom SNPs showed association with BPD. None of the 11 Sequenom SNPs showed association with BPD. | Negative |
| Gene | Statistical Values/Author Comments | Result Category |
|---|---|---|
| ZBED4 | Due to highLD in the region harboring BRD1, we included SNPs located within the ZBED4 gene in this r...... Due to highLD in the region harboring BRD1, we included SNPs located within the ZBED4 gene in this replication analysis. Analysis of genotyped SNPs as well as imputed genotypes showed the strongest association with markers in BRD1. However, due to the high LD we cannot completely rule out ZBED4 as a positional candidate gene for SZ and BPD. More... | Positive |
| BRD1 | The associations reported add further support for the implication of BRD1 with SZ and BPD susceptibi...... The associations reported add further support for the implication of BRD1 with SZ and BPD susceptibility. More... | Positive |
| Disease | SNP | Related Gene(s) | Statistical Values | Description | Result Category |
|---|---|---|---|---|---|
| SZ | rs2239848 | BRD1 | P-value = 0.8, OR=0.9 in UK/DK sample | Nominal significant association with SZ | Positive |
| SZ | rs138880 | BRD1 | P-value = 0.45, OR=1.09 in UK/DK sample | Nominal significant association with SZ | Positive |
| SZ | rs4624 | ZBED4 | P-value = 0.87, OR=0.98 in UK/DK sample | Nominal significant association with SZ | Positive |
| SZ | rs4468 | BRD1 | P-value = 0.61, OR=1.05 in UK/DK sample | Nominal significant association with SZ | Positive |
| SZ | rs6009917 | ZBED4 | P-value = 0.1, OR=2.93 in UK/DK sample | Nominal significant association with SZ | Positive |
| SZ | rs5770755 | ZBED4 | P-value = 0.72, OR=1.04 in UK/DK sample | Nominal significant association with SZ | Positive |
| SZ | rs910799 | ZBED4 | P-value = 0.8, OR=0.97 in UK/DK sample | Nominal significant association with SZ | Positive |
| SZ | rs138820 | BRD1 | P-value = 0.3, OR=1.12 in UK/DK sample | Nominal significant association with SZ | Positive |
| SZ | rs138841 | BRD1 | P-value = 0.46, OR=1.08 in UK/DK sample | Nominal significant association with SZ | Positive |
| SZ | rs138855 | BRD1 | P-value = 0.93, OR=1.01 in UK/DK sample | Nominal significant association with SZ | Positive |
| SZ | rs138864 | BRD1 | P-value = 0.64, OR=1.06 in UK/DK sample | Nominal significant association with SZ | Positive |
| Disease | Markers | Haplotype | Related Gene(s)/Region(s) | Statistical Values | Description | Result Category |
|---|---|---|---|---|---|---|
| SZ | rs4468 rs138841 | TC | BRD1 | Empirical haplotype-specific P-value = 0.043 calculated using PLINK. | 'Protective'' haplotypes over-represented among controls with SZ | Positive |
| SZ | rs4468 - rs138841 - rs138855 | TCG | BRD1 | Empirical haplotype-specific P-value = 0.042 calculated using PLINK. | 'Protective'' haplotypes over-represented among controls with SZ | Positive |
| SZ | rs138864 - rs2239848 | GG | BRD1 | Empirical haplotype-specific P-value = 0.048 calculated using PLINK. | 'Protective'' haplotypes over-represented among controls with SZ | Positive |
| SZ | rs4468 rs138841 | CA | BRD1 | Empirical haplotype-specific P-value = 0.0073 calculated using PLINK. | 'Risk'' haplotypes over-represented among patients with SZ | Positive |
| SZ | rs138820 - rs4468 | TT | BRD1 | Empirical haplotype-specific P-value = 0.041 calculated using PLINK. | 'Protective'' haplotypes over-represented among controls with SZ | Positive |
| SZ | rs138820 - rs4468 | CC | BRD1 | Empirical haplotype-specific P-value = 0.0027 calculated using PLINK. | 'Risk'' haplotypes over-represented among patients with SZ | Positive |
| SZ | rs138820 - rs4468 - rs138841 | TTC | BRD1 | Empirical haplotype-specific P-value = 0.044 calculated using PLINK. | 'Protective'' haplotypes over-represented among controls with SZ | Positive |
| SZ | rs138820 - rs4468 - rs138841 | CCA | BRD1 | Empirical haplotype-specific P-value = 0.0074 calculated using PLINK. | 'Risk'' haplotypes over-represented among patients with SZ | Positive |
| SZ | rs138841 - rs138855 - rs138864 | CGG | BRD1 | Empirical haplotype-specific P-value = 0.0081 calculated using PLINK. | 'Protective'' haplotypes over-represented among controls with SZ | Positive |
| SZ | rs138841 - rs138855 | CG | BRD1 | Empirical haplotype-specific P-value = 0.017 calculated using PLINK. | 'Protective'' haplotypes over-represented among controls with SZ | Positive |
| Disease | Gene | Description | Result Category |
|---|---|---|---|
| SZ | ZBED4 | Due to highLD in the region harboring BRD1, we included SNPs located within the ZBED4 gene in this replication analysis. Analysis of genotyped SNPs as well as imputed genotypes showed the strongest association with markers in BRD1. However, due to the high LD we cannot completely rule out ZBED4 as a positional candidate gene for SZ and BPD. | Positive |
| SZ | BRD1 | The associations reported add further support for the implication of BRD1 with SZ and BPD susceptibility. | Positive |
Copyright: Bioinformatics Lab, Institute of Psychology, Chinese Academy of Sciences Feedback
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Last update: March 31, 2016


