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	Koefoed, P.,2011 PMID: 21897858
Citation	Koefoed, P., O. A. Andreassen, et al. (2011). "Combinations of SNPs related to signal transduction in bipolar disorder." PLoS One 6(8): e23812.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	1355 controls and 607 patients with bipolar disorder
SNP/Region/Marker Size	803 SNPs
Predominant Ethnicity	Caucasian
Population	Danish , Norwegian and WTCCC collections

Detail Info

Sample Diagnosis	DSM
Sample Status	Patient sample This study is based on two independent case-control samples from Norway and Denmark, included in the Scandinavian Collaboration of Psychiatric Etiology (SCOPE). The Danish sample consisted of 220 bipolar patients from the Copenhagen area, 162 bipolar patients in Jutland, and 1133 control participants. The sample from Norway included 222 controls and 225 bipolar patients. Thus, a total of 607 unrelated patients and 1355 unrelated healthy control participants were included. The Norwegian patients had been diagnosed according to the DSM-IV and the Danish patients according to ICD-10. The Norwegian and Danish healthy controls and cases have been described in more detail elsewhere. The Norwegian Scientific-Ethical Committees, the Norwegian Data Protection Agency, the Danish Scientific Committees, and the Danish Data Protection Agency approved the study. All patients gave written informed consent prior to inclusion in the project.
Replication Size	WTCCC data(1998 bipolar patients and 1500 UK blood service control group)
Technique	genotyping
Statistical Method	The statistical significance of single genotype distribution was assessed using the Chi-square or Fisher's exact test, Combinations of genotypes were calculated using array-based mathematical methods, where data are represented geometrically, hereby facilitating parallel processing, which was performed using programs from Genokey (www.genokey.com) and Dyalog (www.dyalog.com).
Result Summary	Four clusters of patient-specific combinations were identified. Permutation tests indicated that some of these combinations might be related to bipolar disorder. The WTCCC bipolar dataset were use for replication, 469 of the 803 SNP were present in the WTCCC dataset either directly (n = 132) or by imputation (n = 337) covering 51 of our selected genes. We found three clusters of patient-specific 3xSNP combinations in the WTCCC dataset. Different SNPs were involved in the clusters in the two datasets. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder.

SNPs reported by this study for BD (count: 4)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs884664	KCNN3			Chi-square test: P-value = 0.01	Significant association was found in genotype association. Significant association was found in genotype association.	Positive
rs2469515	KCNQ3			Chi-square test: P-value = 0.017	Significant association was found in genotype association. Significant association was found in genotype association.	Positive
rs33976516	AVPR1B			Chi-square test: P-value = 0.013	Significant association was found in genotype association. Significant association was found in genotype association.	Positive
rs2179871	CACNG2			Chi-square test: P-value = 0.023	Significant association was found in genotype association. Significant association was found in genotype association.	Positive

Genes reported by this study for BD (count: 4)

Gene	Statistical Values/Author Comments	Result Category
KCNN3	KCNN3_rs884664=2 (two indicate homozygosity for the minor allele) occurred in 45 3-combinations.In 1000 permutation tests, at least one cluster of this type (with at least 37 pseudo-patients) were seen 42 times (p=0.042), two such clusters were seen 3 times (p=0.003), and at least three or more clusters of this type did not occur once(p<0.001).. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogene...... The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder. More...	Positive
KCNQ3	KCNQ3_rs2469515=2)occurred in 32 3-combinations.In 1000 permutation tests, at least one cluster of this type (with at least 37 pseudo-patients) were seen 42 times (p=0.042), two such clusters were seen 3 times (p=0.003), and at least three or more clusters of this type did not occur once(p<0.001).. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogene...... The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder. More...	Positive
CACNG2	CACNG2_rs2179871=2 occurred in 49 3-combinations.In 1000 permutation tests, at least one cluster of this type (with at least 37 pseudo-patients) were seen 42 times (p=0.042), two such clusters were seen 3 times (p=0.003), and at least three or more clusters of this type did not occur once(p<0.001).. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogene...... The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder. More...	Positive
AVPR1B	AVPR1B_rs33976516=1 (one indicate heterozygocity)occurred in 46 3-combinations.In 1000 permutation tests, at least one cluster of this type (with at least 37 pseudo-patients) were seen 42 times (p=0.042), two such clusters were seen 3 times (p=0.003), and at least three or more clusters of this type did not occur once(p<0.001).. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogene...... The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder. More...	Positive