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	Wang, T. Y., 2013 PMID: 24229495
Citation	Wang, T. Y., S. Y. Lee, et al. (2013). "Gender-specific association of the SLC6A4 and DRD2 gene variants in bipolar disorder." Int J Neuropsychopharmacol: 1-12.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	Of the 1335 participants in the study, 400 had BP-I, 493 had BP-II, and 442 were healthy controls.
SNP/Region/Marker Size	2 polymorphisms
Predominant Ethnicity	Mongloid
Population	Chinese
Gender	186 (46.5%) male and 214 (53.5%) female patients with BP-I, 239 (48.5%) male and 254 (51.5%) female patients with BP-II, 325 (73.5%) male and 117 (26.5%) female controls
Age Group	adults : mean age=33.7, SD=12.5 years of BP-I, mean age=32.6, SD=12.0 years of BP-II, mean age=35.3, SD=9.7 years of controls

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	Patients with bipolar disorder were recruited both from outpatient and from inpatient settings. Inclusion criteria were a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edn)-based diagnosis of bipolar disorder, either first-onset or with previous episodes. Patients with major or minor mental illnesses other than bipolar disorder were excluded. 400 BP-I patients, 493 BP-II patients were included.
Technique	The DRD2/ANKK1 Taq-IA functional polymorphism was determined using a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). The 5-HTTLPR functional polymorphisms were genotyped using PCR-RFLP analysis.
Statistical Method	Pearson _2 analysis was used to examine the gender differences. The differences in the genotype frequencies of 5-HTTLPR and DRD2 Taq-IA polymorphisms between men and women in all three groups were calculated using Pearson _2 analysis (two-tailed). Hardy-Weinberg equilibrium was assessed for each group. Logistic regression was used to control the effect of the possible covariates of age when examining the main effects and the effects of gene-to-gene interaction of the DRD2 and SLC6A4 genes in men and women for the risk of BP-I and BP-II in compared with controls. The associations are expressed as odds ratios (OR) with corresponding 95% confidence intervals (CI). P-values are two-tailed, and significance was set at p< 0.05. Bonferroni correction was performed. We adjusted our significant P-value as 0.01.
Result Summary	Logistic regression analysis showed a significant gender-specific association of the DRD2 A1/A1 and the 5-HTTLPR S/S, S/L G , and L G /LG (S+) (p = 0.01) genotypes in men with BP-I (p = 0.002 and 0.01, respectively) and BP-II (p = 0.001 and 0.007, respectively), but not in women. A significant interaction for the DRD2 A1/A1 and 5-HTTLPR S+ polymorphisms was also found only in men with BP-I and BP-II (p = 0.003 and 0.001, respectively). We provide preliminary evidence for a gender-specific effect of the SLC6A4 and DRD2 gene variants for the risk of BP-I and of BP-II. We also found gender-specific interaction between 5-HTTLPR and DRD2 Taq-IA polymorphisms in patients with bipolar disorder.

SNPs reported by this study for BD (count: 1)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs1800497	ANKK1 DRD2	A1/A2		P-value=0.39, X²=4.11; P-value=0.39, X²=4.13 for male; P-value=0.48, X²=3.51 for female; DRD2 A1/A1: P-value=0.003, OR=4.25 for all BP-I, P-value=0.002, OR=7.33 for male BP-I, P-value=0.34, OR=2.25 for female BP-I, P-value<0.001, OR=5.49 for all BP-II, P-value=0.001, OR=8.56 for male BP-II, P-value=0.15, OR=3.33 for female BP-II; DRD2 A1/A2: P-value=0.93, OR=1.02 for all BP-I, P-value=0.38, OR=1.42 for male BP-I, P-value=0.36, OR=0.66 for female BP-I; P-value=0.10, OR=1.56 for all BP-II, P-value=0.16, OR=1.70 for male BP-II, P-value=0.82, OR=1.11 for female BP-II	There was no significant difference in the distribution of t...... There was no significant difference in the distribution of the DRD2 Taq-IA polymorphisms between three groups. It showed a significant association between the DRD2/ANKK1 Taq-IA polymorphisms and patients with BP-I and an association between DRD2 and BP-II. A gender-specific association of the DRD2 polymorphisms and the risk for BP-I and BP-II was also found in the regression model. More...	Positive

Other variants reported by this study for BD (count: 1)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
5HTTLPR	SLC6A4	microsatellite	S/L		P-value=0.01, X²=8.86; P-value=0.01, X²=10.18 for male; P-value=0.71, X²=0.68 for female; 5-HTTLPR S+: P-value=0.03, OR=1.71 for all BP-I, P-value=0.01, OR=2.43 for male BP-I, P-value=0.70, OR=1.17 for female BP-I, P-value=0.003, OR=2.04 for all BP-II, P-value=0.007, OR=2.53 for male BP-II, P-value=0.37, OR=1.43 for female BP-II	The distribution of the 5-HTTLPR genotype was significantly ...... The distribution of the 5-HTTLPR genotype was significantly different between the BP-I, BP-II, and the control groups, and a higher percentage of 5-HTTLPR S+ genotypes was found in the BP-I and BP-II groups. Further analysis of the gender difference revealed that the significantly different distribution of the 5-HTTLPR genotype was only in men. It showed an association between SLC6A4 and BP-II. A gender-specific association of the 5-HTTLPR polymorphisms and the risk for BP-I and BP-II was also found in the regression model. More...	Positive

Genes reported by this study for BD (count: 2)

Gene	Statistical Values/Author Comments	Result Category
DRD2	We provide preliminary evidence for a gender-specific effect of the SLC6A4 and DRD2 gene variants fo...... We provide preliminary evidence for a gender-specific effect of the SLC6A4 and DRD2 gene variants for the risk of BP-I and of BP-II. We also found gender-specific interaction between 5-HTTLPR and DRD2 Taq-IA polymorphisms in patients with bipolar disorder. More...	Positive
SLC6A4	We provide preliminary evidence for a gender-specific effect of the SLC6A4 and DRD2 gene variants fo...... We provide preliminary evidence for a gender-specific effect of the SLC6A4 and DRD2 gene variants for the risk of BP-I and of BP-II. We also found gender-specific interaction between 5-HTTLPR and DRD2 Taq-IA polymorphisms in patients with bipolar disorder. More...	Positive

Gene-gene interactions reported by this study for BD (count: 1)

Gene Group	Markers	Statistical Values	Author Comments	Result Category
SLC6A4 DRD2	rs1800497	For haplotype "S+_A1/A1": P-value=0.001, OR=0.16 for all BP-I, P-value=0.003, OR=0.12 for male BP-I, P-value=0.08, OR=0.19 for female BP-I; P-value<0.001, OR=0.13 for all BP-II, P-value=0.001, OR=0.10 for male BP-II, P-value=0.01, OR=0.15 for female BP-II. For haplotype "S+_A1/A2": P-value=0.70, OR=1.14 for all BP-I, P-value=0.45, OR=0.71 for male BP-I, P-value=0.28, OR=1.82 for female BP-I; P-value=0.55, OR=0.83 for all BP-II, P-value=0.49, OR=0.74 for male BP-II, P-value=0.90, OR=0.07 for female BP-II.	There was a significant interaction between the DRD2/ANKK1 T...... There was a significant interaction between the DRD2/ANKK1 Taq-IA and 5-HTTLPR polymorphisms in BP-I and BP-II. The association between DRD2, 5-HTTLPR, and the gene-to-gene interaction effect for BP-I was found in male patients but not in female patients. There were both main effects and an interaction effect of the DRD2 and SLC6A4 genes for the risk of BP-II in male patients, although not in female patients with BP-II. More...	Positive