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, S. Y., 2012 PMID: 22564712
Citation	Lee, S. Y., S. L. Chen, et al. (2012). "The ALDH2 and 5-HT2A genes interacted in bipolar-I but not bipolar-II disorder." Prog Neuropsychopharmacol Biol Psychiatry.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study & Gene-gene interaction study
Sample Size	Of the 1049 participants in the study, 249 were BP-I patients, 456 were BP-II patients, and 344 were healthy controls.
SNP/Region/Marker Size	2 polymorphisms
Predominant Ethnicity	Mongloid
Population	Chinese
Gender	126 male and 123 female patients with BP-I, 220 male and 236 female patients with BP-II, 234 male and 110 female controls
Age Group	adults : mean age=33.17 (SD=11.65) years of BP-I patients, mean age=31.83 (SD=11.52) years of BP-II patients, mean age=35.33 (SD=9.42) years of controls

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	BP-I and BP-II patients were recruited from outpatient and inpatient settings. All were initially evaluated in an interview by an attending psychiatrist and followed up with a more detailed interview with a clinical psychologist using the Chinese Version of the Modified Schedule of Affective Disorder and Schizophrenia-Life Time, which has good inter-rater reliability, to determine DSM-IV diagnoses. Patients with major mental illnesses, borderline personality disorder, drug dependence, or cognitive disorders other than BP-I and BP-II were excluded.
Technique	genotyping
Statistical Method	The differences in the genotype frequencies of ALDH2 and 5-HT2A-1438A/G polymorphisms between the BP-I, BP-II, and control groups were calculated using Pearson_2 analysis (two-tailed); Hardy-Weinberg equilibrium was assessed for each group. Logistic regression was then used to control the effect of the possible covariates of age and gender when examining the effects of the ALDH2 and 5-HT2A-1438A/G genes and their gene-to-gene interaction effects for the risk of BP-I and BP-II compared with the controls. To identify the significant predictors, backward elimination was used in the logistic regression. The associations are expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Significance was set at pb0.05 (two-tailed).
Result Summary	Logistic regression analysis showed a significant effect of the ALDH2 and the 5-HT2A-A1438G polymorphisms, and a significant interaction effect for the A/G genotypes of the 5-HT2A-A1438G polymorphism and the ALDH211 genotypes (p=0.004) discriminated between bipolar-I patients and controls without bipolar disorder. These polymorphisms, however, were not associated with bipolar-II disorder. LIMITATIONS: The significant differences of age and gender between patients and controls limit the comparison, although statistical adjustments were made for them. Our findings provide initial evidence that the ALDH2 and 5-HT2A genes interact in bipolar-I but not in bipolar-II disorder. Our findings suggest a unique genetic distinction between bipolar-I and bipolar-II.

Other variants reported by this study for BD (count: 2)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
HTR2A -1438A/G	HTR2A	point mutation	A/G		allelic P-value = 0.37, X²=0.82, genotypic P-value = 0.67, X²=0.80 for BP-I vs. controls; allelic P-value = 0.31, X²=1.05, genotypic P-value = 0.45, X²=1.62 for BP-II vs. controls; allelic P-value = 0.53, X²=1.27, genotypic P-value = 0.72, X²=2.09 for BP-I vs. BP-II vs. controls.	distributions of the 5-HT2A-1438A/G polymorphism were not as...... distributions of the 5-HT2A-1438A/G polymorphism were not associated with either BP-I or BP-II More...	Negative
ALDH2 12 allele	ALDH2	others			allelic P-value = 0.07, X²=3.35, genotypic P-value = 0.18, X²=3.48 for BP-I vs. controls; allelic P-value = 0.97, X²=0.002, genotypic P-value = 0.71, X²=0.68 for BP-II vs. controls; allelic P-value = 0.11, X²=4.42, genotypic P-value = 0.28, X²=5.11 for BP-I vs. BP-II vs. controls.	distributions of the ALDH2 were not associated with either B...... distributions of the ALDH2 were not associated with either BP-I or BP-II More...	Negative

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

Gene	Statistical Values/Author Comments	Result Category
ALDH2	ALDH211: P-value = 0.002, OR(95% CI)=4.48(1.76-11.40) in BP-I, P-value = 0.425, OR(95% CI)=1.34(0.66-2.73) in BP-II. The regression showed a significant association of the ALDH2 with BP-I only. The regression showed a significant association of the ALDH2 with BP-I only.	Positive
HTR2A	5-HT2A-1438A/G A/A: P-value = 0.010, OR(95% CI)=3.13(1.31-7.49) in BP-I, P-value = 0.209, OR(95% CI)=1.48(0.80-2.74) in BP-II; 5-HT2A-1438A/G A/G: P-value = 0.019, OR(95% CI)=2.81(1.18-6.66) in BP-I, P-value = 0.165, OR(95% CI)=1.53(0.84-2.78) in BP-II. The regression showed a significant association of the 5-HT2A-1438A/G polymorphisms with BP-I only. The regression showed a significant association of the 5-HT2A-1438A/G polymorphisms with BP-I only.	Positive

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

Gene Group	Markers	Statistical Values	Author Comments	Result Category
ALDH2 HTR2A	ALDH2_11* - HTR2A_-1438A/GA/A; ALDH2_11* - HTR2A_-1438A/GA/G	For markers "ALDH2_11* - HTR2A_-1438A/GA/A", P-value = 0.015, OR(95% CI)=0.27(0.09-0.77) in BP-I, P-value = 0.680, OR(95% CI)=0.83(0.35-1.98) in BP-II. For markers "ALDH2_11* - HTR2A_-1438A/GA/G", P-value = 0.005, OR(95% CI)=0.22(0.08-0.64) in BP-I, P-value = 0.294, OR(95% CI)=0.64(0.28-1.47) in BP-II	a significant interaction between the ALDH2 and 5-HT2A-1438A...... a significant interaction between the ALDH2 and 5-HT2A-1438A/G polymorphisms was detected in BP-I. No associations were detected between the ALDH2 and 5-HT2A-1438A/G polymorphisms and BP-II. More...	Positive