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	Glaser, B.,2005(a) PMID: 15940297
Citation	Glaser, B., G. Kirov, et al. (2005). Identification of a potential bipolar risk haplotype in the gene encoding the winged-helix transcription factor RFX4. Mol Psychiatry 10(10): 920-927.
Disease Type	Bipolar I Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	347 cases, 374 controls
SNP/Region/Marker Size	10 SNPs
Predominant Ethnicity	Caucasian
Population	British
Gender	254 males, 422 females in BPIcases and 256 males, 434 females in controls
Age Group	Adults : Mean age(SD)(year):48(13) in BPI cases and 42(13) in controls

Detail Info

Sample Diagnosis	DSM
Sample Status	Our case-control panel included 676 unrelated British Caucasian patients meeting DSM IV criteria for BPI disorder. On average, probands suffered from more than six previous episodes of depression (mean 6.6, SD 9.9) and six previous episodes of mania (mean 6.0, SD 6.9). Approximately 74% of them had experienced symptoms of psychosis and 35% of them mood incongruent psychotic symptoms. The onset of impairment commenced on average at 26 years (SD 10 years). All cases were recruited from psychiatric outpatients clinics in South Wales and the Midlands of England and were interviewed by a trained psychiatrist using either SADS-L (Schedule for Affective Disorder and Schizophrenia,Lifetime Version)28 or SCAN (Schedules for Clinical Assessment in Neuropsychiatry).Unrelated British Caucasian controls were either recruited from the Blood Transfusion Service in Wales and England (580 individuals) or were patients, who were attending a family medical practitioner in South Wales for nonpsychiatric reasons (GP controls, 110 individuals).Our total comparison group comprised 690 individuals, which were group-matched with the BPI patients for age and sex.To facilitate LD mapping we employed a twostage screening strategy and genotyped our full sample in two subsets: a screening subset (subset I:347 cases, 374 controls) and a follow-up sample(subset II: 329 cases, 316 controls).
Replication Size	329 cases, 316 controls
Technique	genotyping
Statistical Method	Allele- and genotype-wise biallelic marker frequencies between case and control individuals were compared using a standard X²-test, microsatellite marker frequencies were compared using a Monte-Carlo-algorithm as implemented in CLUMP.
Result Summary	Through analysis of 10 haplotype-tagging markers and using a two-stage approach (subset I: 347 cases, 374 controls; subset II: 329 cases, 316 controls), we identified a haplotype at rs10778502 and ss24735177, which showed nominally significant disease association in our full sample (haplotype-specific P=0.002, global P=0.017; subset I: haplotype-specific P=0.0002, global P=0.0008; subset II: haplotype-specific P=0.572, global P=0.109). Evidence for potential disease association with mutations across the RFX4 region came also from the analysis of the nearby microsatellite D12S2072 (empirical P=0.009 in our full sample). Investigation of RFX4 brain cDNA tagged by rs10778502 provided evidence for significant allelic differences in expression (P<0.001), where some of the variance was accounted for by the genotype at ss24735177. Our findings thus indicate the potential functional relevance of the associated haplotype and now require replication in independent samples.

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

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs10778502 - ss24735177		RFX4	Haplotypic association:for Subset I, P-value(C-Ins)=0.0002, global P-value = 0.0008; for Subset II, P-value(C-Ins)=0.572, global P-value = 0.109; for Subset I+II, P-value(C-Ins)=0.002, global P-value = 0.017	Strongest evidence for disease association in subset I, but ...... Strongest evidence for disease association in subset I, but no replication of the signal could be observed in subset II, however, when the data from the two subsets were combined significant association with BPD remained. More...	Positive
rs10778502 - ss24735177 - D12S2072		RFX4	Haplotypic association:global P-value = 0.04	Significant association was found in global P-value. Significant association was found in global P-value.	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
RFX4 D12S2072	RFX4	microsatellite			Allelic association:empirical P-value = 0.009 for all sample, LD with alleles at rs10778502 and ss24735177(D'=0.83-0.99)	The alleles at the polymorphism were significantly associate...... The alleles at the polymorphism were significantly associated with the BPD. More...	Positive

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