BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

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Study Report

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Basic Info

Reference	Yosifova, A.,2011 PMID: 21771265
Citation	Yosifova, A., T. Mushiroda, et al. (2011). "Genome-wide association study on bipolar disorder in the Bulgarian population." Genes Brain Behav 10(7): 789-797.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Genome-wide association study
Sample Size	188 bipolar disorder patients and 376 control subjects
SNP/Region/Marker Size	497,732 SNPs
Predominant Ethnicity	Caucasian
Population	Bulgarian
Gender	Male/female:66/122 in BD patients and 165/211 in controls for GWAS sample set;53/69 in BD patients and 183/145 in controls for replication set

Detail Info

Sample Diagnosis	DSM
Sample Status	For the GWAS, peripheral blood samples from 188 unrelated Bulgarian individuals with BAD were collected from the University Psychiatric Clinics in Plovdiv, Sofia and Radnevo in Bulgaria. The control group includes 376 unrelated healthy individuals. For the replication study, a total of 450 independent, non-overlapping participants were examined. Of these, 122 were BAD cases, recruited from the Psychiatric Clinics and Dispensaries in Plovdiv, Radnevo, Sofia, Blagoevgrad and Russe,and 328 were controls.
Replication Size	122 bipolar disorder patients and 328 control subjects
Technique	For the GWAS:Genotyping(Illumina Human-Hap550v3 Genotyping BeadChip);for replication study:PCR and sequencing
Statistical Method	Differences between the case and control groups in GWAS and in the replication study were tested by a two-tailed Fisher's exact test in dominant, recessive and allelic models.To determine the overall evidence of association, Mantel-Haenszel test statistics were applied to the two datasets.
Result Summary	Although our study did not show any association P value that achieved genome-wide significance, and none of the top 100 SNPs reached the Bonferroni-corrected P value in the replication study, the plausible involvement of some variants cannot be entirely discarded. Three polymorphisms, rs8099939 [P = 2.12 x 10(-6), odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.43-2.67] in GRIK5, rs6122972 (P = 3.11 x 10(-6), OR = 2.02, 95% CI = 1.46-2.80) in PARD6B and rs2289700 (P = 9.14 x 10(-6), OR = 2.13, 95% CI = 1.53-2.95) in CTSH remained associated at a similar level after Mantel-Haenszel test for combining the results from the genome-wide and replication studies. A modest association was also detected for SNP rs1012053 (GWAS P = 4.50 x 10(-2)) in DGKH, which has already been reported as the most significant variant in a previous genome-wide scan on bipolar disorder. However, further studies using larger datasets are needed to identify variants with smaller effects that contribute to the risk of bipolar disorder.

SNPs reported by this study for BD (count: 14)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs16970287	CTSH	A>G		GWAS P-value = 0.00000477, OR(95%CI)=2.75(1.75-4.33); Replication P-value = 0.257, OR(95%CI)=1.39(0.82-2.36); Mantel-Haenszel P-value = 0.000027, OR(95%CI)=2.14(1.52-3.00)	Suggestive association was found. Suggestive association was found.	Trend
rs2289700	CTSH	G>A		GWAS P-value = 0.0000026, OR(95%CI)=2.7(1.74-4.19); Replication P-value = 0.171, OR(95%CI)=1.47(0.88-2.45); Mantel-Haenszel P-value = 0.00000914, OR(95%CI)=2.13(1.53-2.95)	Suggestive association was found. Suggestive association was found.	Trend
rs3123209	TCERG1L	G>A		GWAS P-value = 0.0000229, OR(95%CI)=2.63(1.67-4.15); Replication P-value = 0.101, OR(95%CI)=1.57(0.89-2.75); Mantel-Haenszel P-value = 0.0000756, OR(95%CI)=2.06(1.45-2.94)	Suggestive association was found. Suggestive association was found.	Trend
rs4317369	GABRA1			GWAS P-value = 0.0000309, OR(95%CI)=2.1(1.45-3.04); Replication P-value = 0.629, OR(95%CI)=1.19(0.62-2.30); Mantel-Haenszel P-value = 0.00399, OR(95%CI)=1.51(1.14-2.00)	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs10507408		A>G		GWAS P-value = 0.0000539, OR(95%CI)=3.64(1.89-7.00); Replication P-value = 0.102, OR(95%CI)=1.76(0.89-3.46); Mantel-Haenszel P-value = 0.0000488, OR(95%CI)=2.58(1.61-4.15)	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs10875032	PTBP2	G>T		GWAS P-value = 0.00000899, OR(95%CI)=2.97(1.81-4.88); Replication P-value = 0.03, OR(95%CI)=1.94(1.07-3.52); Mantel-Haenszel P-value = 0.0000967, OR(95%CI)=2.76(1.88-4.05)	Suggestive association was found. Suggestive association was found.	Trend
rs11129950	CCK	A>G		GWAS P-value = 0.00000883, OR(95%CI)=2.78(1.75-4.40); Replication P-value = 0.098, OR(95%CI)=1.4(0.85-2.32); Mantel-Haenszel P-value = 0.0000218, OR(95%CI)=1.99(1.42-2.79)	Suggestive association was found. Suggestive association was found.	Trend
rs11951528	GABRA1			GWAS P-value = 0.0000199, OR(95%CI)=2.14(1.48-3.10); Replication P-value = 0.527, OR(95%CI)=1.24(0.65-2.39); Mantel-Haenszel P-value = 0.00283, OR(95%CI)=1.5(1.13-1.98)	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs4447895	CHRNA9			GWAS P-value = 0.0000583, OR(95%CI)=2.98(1.70-5.24); Replication P-value = 0.278, OR(95%CI)=1.31(0.72-2.38); Mantel-Haenszel P-value = 0.000168, OR(95%CI)=2.13(1.41-3.20)	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs6122972	PARD6B	A>G		GWAS P-value = 0.00000254, OR(95%CI)=2.76(1.75-4.35); Replication P-value = 0.078, OR(95%CI)=1.5(0.92-2.44); Mantel-Haenszel P-value = 0.00000311, OR(95%CI)=2.02(1.46-2.80)	Suggestive association was found. Suggestive association was found.	Trend
rs8099939	GRIK5	G>T		GWAS P-value = 0.00000146, OR(95%CI)=2.53(1.65-3.88); Replication P-value = 0.097, OR(95%CI)=1.45(0.90-2.34); Mantel-Haenszel P-value = 0.00000212, OR(95%CI)=1.95(1.43-2.67)	Suggestive association was found. Suggestive association was found.	Trend
rs8109263	ZNF626	G>T		GWAS P-value = 0.00000199, OR(95%CI)=3.52(2.07-6.00); Replication P-value = 0.229, OR(95%CI)=1.42(0.82-2.47); Mantel-Haenszel P-value = 0.0000408, OR(95%CI)=2.35(1.60-3.44)	Suggestive association was found. Suggestive association was found.	Trend
rs10491291	FSTL4	C>T		GWAS P-value = 0.00000482, OR(95%CI)=2.36(1.59-3.51); Replication P-value = 0.471, OR(95%CI)=1.21(0.76-1.91); Mantel-Haenszel P-value = 0.0000953, OR(95%CI)=1.72(1.28-2.31)	Suggestive association was found. Suggestive association was found.	Trend
rs10476364	GABRA6			GWAS P-value = 0.0000139, OR(95%CI)=2.14(1.48-3.10); Replication P-value = 0.628, OR(95%CI)=1.21(0.63-2.32); Mantel-Haenszel P-value = 0.00184, OR(95%CI)=1.55(1.17-2.05)	No significant association was observed in BD. No significant association was observed in BD.	Negative

Genes reported by this study for BD (count: 11)

Gene	Statistical Values/Author Comments	Result Category
FSTL4	Suggestive association of this gene was found. Suggestive association of this gene was found.	Trend
CCK	Suggestive association of this gene was found. Suggestive association of this gene was found.	Trend
TCERG1L	Suggestive association of this gene was found. Suggestive association of this gene was found.	Trend
ZNF626	Suggestive association of this gene was found. Suggestive association of this gene was found.	Trend
CHRNA9	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
PTBP2	Suggestive association of this gene was found. Suggestive association of this gene was found.	Trend
GABRA6	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
GRIK5	Suggestive association of this gene was found. Suggestive association of this gene was found.	Trend
PARD6B	Suggestive association of this gene was found. Suggestive association of this gene was found.	Trend
CTSH	Suggestive association of this gene was found. Suggestive association of this gene was found.	Trend
GABRA1	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative