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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Basic Info

Reference	Lee, M. T.,2011 PMID: 20386566
Citation	Lee, M. T., C. H. Chen, et al. (2011). "Genome-wide association study of bipolar I disorder in the Han Chinese population." Mol Psychiatry 16(5): 548-556.
Disease Type	Bipolar I Disorder
Study Design	case-control
Study Type	Genome-wide association study
Sample Size	1000 bipolar I patients and 1000 controls
SNP/Region/Marker Size	516,919 SNPs
Predominant Ethnicity	Mongloid
Population	Chinese

Detail Info

Sample Diagnosis	DSM
Sample Status	A Taiwan Bipolar Consortium was established for this study by ATAC with members from the Institute of Biomedical Sciences, Academia Sinica and 25 psychiatric departments of general hospitals and psychiatric institutions in Taiwan. A total of 1409 unrelated bipolar I patients were consecutively recruited from inpatient units of these psychiatric departments and institutions, including 665 (47.2%) males and 744 females (52.8%). All of them were diagnosed according to DSM-IV criteria16 for bipolar I disorder with at least one inpatient treatment for manic episode, and nearly all of them (96.3%) had recurrent episodes of mania. Patients with other psychotic and affective disorders were excluded. Only the Han-Chinese population, which accounted for 98% of the population in Taiwan, was considered for the recruitment of patients in this study. The control group (N= 2000, with nearly equal proportions of men and women) was randomly selected from the Han-Chinese Cell and Genome Bank in Taiwan reported previously. In brief, more than 3300 healthy controls were recruited via a stratified, 3-staged probability clustering sampling scheme through the registry of all the 329 nonaboriginal townships or city districts in Taiwan.
Replication Size	409 cases and 1000 controls
Technique	genotyping(Illumina HumanHap550-Duo BeadChip)
Statistical Method	GWA analysis was performed using genotype, allele-type and Cochran-Armitage trend test along with tests considering dominant and recessive inheritance models.Two-point analysis was performed using logistic regression model, regressing the affected status on two SNPs and their interaction.Multi-point/haplotype analysis was performed using the Haplotype Score Test.
Result Summary	Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 alpha-N-acetyl- neuraminide alpha-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 x 10(-7) (rs2709736) and 6.05 x 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 x 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, beta-2 subunit) gene (rs11013860, P=5.15 x 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 x 10(-5) and P=1.48 x 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.

SNPs reported by this study for BD (count: 8)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs1323038		A/T		Genome-wide association: in joint analysis, genotype, P-value = 1.56E-05	No significant association was observed. No significant association was observed.	Negative
rs2073831	BTF3P11 KCTD12	C/T		Genome-wide association: in joint analysis, C vs. T, P-value = 9.74E-06; genotype, P-value = 1.35E-05	Suggestive association was found. Suggestive association was found.	Trend
rs11013860	CACNB2	A/C		Genome-wide association: in joint analysis, CC vs. AA+AC, P-value = 5.15E-05; genotype , P-value = 5.54E-04	No significant association was observed. No significant association was observed.	Negative
rs576026	ADAMTSL1	A/G		Genome-wide association: in joint analysis, AA vs. AG+GG, P-value = 1.51E-03; genotype , P-value = 0.02476	No significant association was observed. No significant association was observed.	Negative
rs7174854	C15orf32 ST8SIA2	A/T		Genome-wide association: in joint analysis, A vs. T, P-value = 3.50E-06; genotype, P-value = 3.79E-06	Suggestive association was found. Suggestive association was found.	Trend
rs2709722	RPL23P8 SP8	C/T		Genome-wide association: in joint analysis, TT&CT vs. CC, P-value = 4.65E-06; genotype , P-value = 6.59E-05	Suggestive association was found. Suggestive association was found.	Trend
rs2709736	RPL23P8 SP8	A/C		Genome-wide association: in joint analysis, AA&AG vs. GG, P-value = 4.87E-07; genotype , P-value = 1.36E-05	Suggestive association was found. Suggestive association was found.	Trend
rs8040009	C15orf32 ST8SIA2	T/C		Genome-wide association: in joint analysis, T vs. C, P-value = 6.05E-06; genotype , P-value = 6.38E-06	Suggestive association was found. Suggestive association was found.	Trend

Genes reported by this study for BD (count: 5)

Gene	Statistical Values/Author Comments	Result Category
ADAMTSL1	No significant associations were detected in BPI patients. No significant associations were detected in BPI patients.	Negative
ST8SIA2	SNPs close to ST8 a-Nacetyl- neuraminide a-2, 8-sialyltransferase (ST8SIA2) are associated with Bip...... SNPs close to ST8 a-Nacetyl- neuraminide a-2, 8-sialyltransferase (ST8SIA2) are associated with Bipolar I Disorder. More...	Positive
SP8	SNPs close to specificity protein 8 (SP8) are associated with Bipolar I Disorder. SNPs close to specificity protein 8 (SP8) are associated with Bipolar I Disorder.	Positive
CACNB2	No significant associations were detected in BPI patients. No significant associations were detected in BPI patients.	Negative
KCTD12	Suggestive association of this gene was found. Suggestive association of this gene was found.	Trend