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	Goes, F. S.,2011 PMID: 21637803
Citation	Goes, F. S., M. Rongione, et al. (2011). "Exonic DNA sequencing of ERBB4 in bipolar disorder." PLoS One 6(5): e20242.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	1,001 BP cases and 1,033 controls
SNP/Region/Marker Size	2 variants
Predominant Ethnicity	Caucasian
Population	American

Detail Info

Sample Diagnosis	DSM
Sample Status	Cases were selected from the 1,001 BP cases and 1,033 controls of European-American descent genotyped through the GAIN consortium by the Bipolar Genome Study (BiGS). All cases were interviewed with the Diagnostic Interview for Genetic Studies (DIGS) and best-estimate diagnoses were made by two research psychiatrists or PhD psychologists. Among the BP cases, we initially selected for sequencing the 189 subjects from the GAIN BP sample who had a lifetime history of moodincongruent psychosis as previously defined. Briefly, subjects were classified as cases with mood-incongruent psychotic bipolar disorder if they had a lifetime history of running commentary auditory hallucinations, or passivity delusions such as delusions of being controlled, or delusions of thought insertion, withdrawal, or broadcasting. Subjects were also included if their psychotic symptoms during their most severe depression or mania were judged by the interviewer to be inconsistent with typical depressive or manic themes. Of the 189 subjects, one subject was sequenced in duplicate, and DNA for one subject was unavailable, leading to a final count of 188 subjects sequenced across the ERBB4 gene. In our association study we genotyped all 189 cases as well as 810 non mood-incongruent BP cases and 999 healthy controls from the GAIN BP consortium sample. These controls were previously ascertained using an Internet based adaption of the Composite International Diagnostic Interview-Short Form (CIDISF). Controls were selected to have no self-reported history of hallucinations, bipolar disorder, or schizophrenia, and no history of sufficient lifetime depressive symptoms to meet DSM-IV criteria for major depressive disorder.
Technique	genotyping
Statistical Method	Based on a scree plot, we selected the top two principal components to include as covariates in our association analysis.We performed association analyses using additive and dominant models.
Result Summary	We genotyped this variant in the GAIN BP case-control samples and found a marginally significant association with mood-incongruent psychotic BP compared with controls (additive model: OR = 1.64, P-value = 0.055; dominant model: OR = 1.73. P-value = 0.039). In conclusion, we found no rare variants of clear deleterious effect, but did uncover a modestly associated novel variant that could affect alternative splicing of ERBB4. However, the modest sample size in this study cannot definitively rule out a role for rare variants in bipolar disorder and studies with larger sample sizes are needed to confirm the observed association.

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
ERBB4 SNV7 G>A	ERBB4	point mutation	G>A		In cases with mood-incongruent psychotic BP compared with controls: in a dominant model(OR = 1.73, P-value = 0.039) and in an additive model (OR= 1.64, P-value = 0.055).	Significant associations were found. Significant associations were found.	Positive
ERBB4 SNV8 A insertion/deletion	ERBB4	insertion/deletion	A insertion/deletion		In case-control:P-value = 0.87	No significant association was observed. No significant association was observed.	Negative

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