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	Magno, L. A.,2011 PMID: 21621268
Citation	Magno, L. A., C. V. Santana, et al. (2011). "Genetic variations in FOXO3A are associated with Bipolar Disorder without confering vulnerability for suicidal behavior." J Affect Disord 133(3): 633-637.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	273 BD patients and 264 control subjects
SNP/Region/Marker Size	4 SNPs
Predominant Ethnicity
Population	Brazilian
Gender	30.6% males in BD patients and 33.6% males in controls
Age Group	Adults : Mean age(SD)(year):males: 41.4(12.9) and females: 40.5(12.3) in BD patients;males: 57.5(13.4) and females:58.13(13.8) in controls

Detail Info

Sample Diagnosis	DSM
Sample Status	The case group consisted of 273 BD patients type I or II.These patients were randomly selected from the Bipolar Treatment Unit of the Instituto de Previdencia do Estado de Minas Gerais during a 2-year period. The BD patients sample was divided between suicide attempters (45.2% had a history of suicide attempt) and among them separated into violent (42.4%) or non-violent. Suicide behavior was assessed as previously described (Magno et al., 2010). A suicide attempt was defined as a conscious intent of the patient to end his/her own life, through means that the patient thought could have resulted in death. The controls consisted of 264 healthy unrelated volunteers.
Technique	genotyping
Statistical Method	The genetic frequency and association analysis between the comparison groups were performed with UNPHASED v.3.121 (Dudbridge, 2008). This software implements a retrospective likelihood test (the probability of observing genotypes given phenotypes) using a multinomial logistic model. To evaluate pairwise linkage disequilibrium (LD) matrices between each SNP, haplotype associations and genotype deviation from the Hardy-Weinberg equilibrium (HWE), HAPLOVIEW v.4.2 was used (Barrett et al., 2005). We chose D_ (0-1.0) to describe the magnitude of LD. SPSS v.15.0 and GraphPad Prism v.5 were used for statistical analysis and graph design, respectively.
Result Summary	RESULTS: Three SNPs (rs1536057, rs2802292 and rs1935952) were associated with BD, but none was positively linked with suicidal behavior. LIMITATION: A systematic evaluation within the whole FOXO3A gene and drug treatment in patients was not performed. CONCLUSIONS: These data suggest that FOXO3A is a novel susceptibility locus for BD, but not for suicidal behavior in BD patients. These results may contribute to a better understanding of the BD genetics.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs3813498	FOXO3 SUMO2P8	C/G		Chi-square tests: genotype: P-value > 0.05; allele: P-value > 0.05	No significant association was observed. No significant association was observed.	Negative
rs2802292	FOXO3	G/T		Chi-square tests: genotype: X²=7.03, P-value = 0.0297; allele: X²=4.30, P-value = 0.0381	Significant association was found . Significant association was found .	Positive
rs1935952	FOXO3	T/C		Chi-square tests: genotype: X²=6.59, P-value = 0.0370; allele: X²=6.39, P-value = 0.0114	Significant association was found . Significant association was found .	Positive
rs1536057	FOXO3	G/A		Chi-square tests: genotype: X²=11.11, P-value = 0.0038; allele: X²=7.42, P-value = 0.0064	Significant association was found . Significant association was found .	Positive

Haplotypes reported by this study for BD (count: 9)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs1536057 - rs2802292 - rs3813498 - rs1935952	G-T-T-G	FOXO3	Chi-square tests:X<sup>2</sup>=0.677, P-value = 0.4107	No significant association was found . No significant association was found .	Negative
rs1536057 - rs2802292 - rs3813498 - rs1935952	G-G-T-C	FOXO3	Chi-square tests:X<sup>2</sup>=1.327, P-value = 0.2493	No significant association was found . No significant association was found .	Negative
rs1536057 - rs2802292 - rs3813498 - rs1935952	G-G-T-G	FOXO3	Chi-square tests:X<sup>2</sup>=1.064, P-value = 0.3023	No significant association was found . No significant association was found .	Negative
rs1536057 - rs2802292 - rs3813498 - rs1935952	G-T-C-G	FOXO3	Chi-square tests:X<sup>2</sup>=1.537, P-value = 0.2151	No significant association was found . No significant association was found .	Negative
rs1536057 - rs2802292 - rs3813498 - rs1935952	G-T-T-C	FOXO3	Chi-square tests:X<sup>2</sup>=2.416, P-value = 0.1201	No significant association was found . No significant association was found .	Negative
rs1536057 - rs2802292 - rs3813498 - rs1935952	A-G-C-G	FOXO3	Chi-square tests:X<sup>2</sup>=3.44, P-value = 0.0636	No significant association was found . No significant association was found .	Negative
rs1536057 - rs2802292 - rs3813498 - rs1935952	A-G-T-C	FOXO3	Chi-square tests:X<sup>2</sup>=0.041, P-value = 0.8403	No significant association was found . No significant association was found .	Negative
rs1536057 - rs2802292 - rs3813498 - rs1935952	A-G-T-G	FOXO3	Chi-square tests:X<sup>2</sup>=5.886, P-value = 0.0153	Significant association was found in individual P-value. Significant association was found in individual P-value.	Positive
rs1536057 - rs2802292 - rs3813498 - rs1935952	G-G-C-G	FOXO3	Chi-square tests:X<sup>2</sup>=0.307, P-value = 0.5796	No significant association was found . No significant association was found .	Negative

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