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(b) PMID: 15389760
Citation	Glaser, B., G. Kirov, et al. (2005). Linkage disequilibrium mapping of bipolar affective disorder at 12q23-q24 provides evidence for association at CUX2 and FLJ32356. Am J Med Genet B Neuropsychiatr Genet 132B(1): 38-45.
Disease Type	Bipolar I Disorder
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	Case-control sample consists of 347 unrelated British patients and 374 unrelated British Caucasian controls;parent-offspring trio sample included 110 Caucasian BPI patients and their parents .
SNP/Region/Marker Size	22 polymorphisms
Predominant Ethnicity	Caucasian
Population	British
Gender	Case-control sample:151 males, 196 females in cases and 160 males,214 females in controls;Parent-offspring trio sample:49 males, 61 females
Age Group	Adults : Mean age(SD)(year):48.9(11.3) in BPI cases and 46.1(12.7) in controls in case-control sample,34.3(8.7) in BPI patients and 64.6(9.9)of father,62.0(9.5) of mother in their parents in parent-offspring trio sample

Detail Info

Sample Diagnosis	DSM
Sample Status	On average,patients suffered from more than six previous episodes of depression (mean 6.58, SD 9.79) and more than seven previous episodes of mania (mean 7.17, SD 10.80). Seventy-one percent of probands had experienced symptoms of psychosis and 32% mood incongruent psychotic symptoms. The onset of impairment started on average at 26.50 years (SD 10.93).All cases were recruited from psychiatric outpatients clinics in South Wales and the Midlands of England and interviewed by a trained psychiatrist using either Schedule for affective disorder and schizophrenia, lifetime version (SADS-L)[Endicott and Spitzer, 1978] or Schedules for clinical assessment in neuropsychiatry (SCAN) [Wing et al., 1990].Consensus best estimate lifetime diagnoses according to DSM IV were made on the basis of all available clinical information by two experienced clinicians (including NC in each case).Unrelated British Caucasian controls were collected from the Blood Transfusion Service in Wales and groupmatched with patients for age and sex.To facilitate our two-stage strategy, our sample was divided into two sub-samples: Sample I (161 BPI, 188 controls) and Sample II(186 BPI, 186 controls).Our parent-offspring trio sample included 110 Caucasian BPI patients and their parents,all of European descent, which were collected with identical methods as described for the cases samples.
Technique	genotyping
Statistical Method	Marker allele differences for microsatellites in pooled DNA(product of estimated marker frequencies according to peak height number of individuals in pool) and from individual genotyping were statistically assessed with CLUMP[Sham and Curtis, 1995], a Monte Carlo based permutation test. Allele- and genotype-wise biallelic marker frequencies between cases and controls were compared using a standard X²-test. The transmission disequilibrium test (TDT) [Spielman et al., 1993] was used to analyze the data from the trios sample.Haplotype frequencies for different marker combinations in the case-control association sample were computed with the EHPlus program [Zhao et al., 2000] which yields maximum likelihood estimates according to an estimation-maximization algorithm
Result Summary	Two SNPs (rs3847953 and rs933399) and an insertion/deletion with putative functional relevance (which are in high LD with each other and with the microsatellite marker) showed significant or nearly significant association with bipolar disorder after Bonferroni-correction (reaching nominal P values from P = 0.002 to P = 0.005). In a sample of 110 UK Caucasian parent-offspring trios there was a trend for an over transmission in the same direction that failed to meet conventional levels of statistical significance. Our data provide evidence for association between bipolar mood disorder and markers on chromosome 12q23-q24 but need replication in independent samples.

SNPs reported by this study for BD (count: 12)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs3742006	CUX2	C/G		For Sample I, allelic association: X²=5.5, P-value = 0.02, OR(95%CI)=0.6(0.4-0.9); genotypic association: X²=6.63, P-value = 0.04	Significant association was observed in both allelic associa...... Significant association was observed in both allelic association and genotypic association. More...	Positive
rs3184504	SH2B3	T/C		For Sample I+II, allelic association: X²=3.15, P-value = 0.08, OR(95%CI)=1.2(1.0-1.5); genotypic association: X²=4.23, P-value = 0.12	No significant association was observed. No significant association was observed.	Negative
rs3803170	SH2B3	G/A		For Sample I, allelic association: X²=0, P-value = 0.96, OR(95%CI)=1(0.7-1.4); genotypic association: X²=8.72, P-value = 0.01	Significant association was observed in genotypic associatio...... Significant association was observed in genotypic association. More...	Positive
rs3742007	CUX2	T/C		For Sample I, allelic association: X²=0.49, P-value = 0.48, OR(95%CI)=0.9(0.6-1.3); genotypic association: X²=3.36, P-value = 0.19	No significant association was observed. No significant association was observed.	Negative
rs2283358	SH2B3	A/G		For Sample I, allelic association: X²=0.05, P-value = 0.83, OR(95%CI)=1(0.7-1.4); genotypic association: X²=8.57, P-value = 0.01	Significant association was observed in genotypic associatio...... Significant association was observed in genotypic association. More...	Positive
rs4766572		A/G		For Sample I, allelic association: X²=2.44, P-value = 0.12, OR(95%CI)=0.8(0.5-1.1); genotypic association: X²=3.39, P-value = 0.18	No significant association was observed. No significant association was observed.	Negative
rs933305	CUX2	T/C		For Sample I+II, allelic association: X²=5.32, P-value = 0.02, OR(95%CI)=0.7(0.6-10); genotypic association: X²=5.4, P-value = 0.07	Significant association was observed in allelic association. Significant association was observed in allelic association.	Positive
rs933399	FAM109A	A/G		For Sample I+II, allelic association: X²=8.25, P-value = 0.004, OR(95%CI)=0.7(0.6-0.9); genotypic association: X²=8.75, P-value = 0.01. For family based study, TDT: X²=0.24, P-value = 0.69.	Significant association was observed in both allelic associa...... Significant association was observed in both allelic association and genotypic association, but No significant association was observed in family based study. More...	Positive
rs3809272	FAM109A	A/G		For Sample I, allelic association: X²=0.07, P-value = 0.79, OR(95%CI)=1(0.8-1.4); genotypic association: X²=0.35, P-value = 0.84	No significant association was observed. No significant association was observed.	Negative
rs3840795	FAM109A	D/I		For Sample I+II, allelic association: X²=7.56, P-value = 0.005, OR(95%CI)=0.7(0.5-0.9); genotypic association: X²=7.73, P-value = 0.02. For family based study, TDT: X²=0.67, P-value < 0.2.	Significant association was observed in both allelic associa...... Significant association was observed in both allelic association and genotypic association, but No significant association was observed in family based study. More...	Positive
rs3843673	CUX2	C/T		For Sample I, allelic association: X²=5.55, P-value = 0.02, OR(95%CI)=0.7(0.5-0.9); genotypic association: X²=6.48, P-value = 0.04	Significant association was observed in both allelic associa...... Significant association was observed in both allelic association and genotypic association. More...	Positive
rs3847953	CUX2	A/G		For Sample I+II, allelic association: X²=9.24, P-value = 0.002, OR(95%CI)=0.7(0.5-0.9); genotypic association: X²=11.49, P-value = 0.003. For family based study, TDT: X²=0.12, P-value = 0.73.	Significant association was observed in both allelic associa...... Significant association was observed in both allelic association and genotypic association, but No significant association was observed in family based study. More...	Positive

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

Gene	Statistical Values/Author Comments	Result Category
FAM109A	In summary, we have provided evidence for association between BPD and polymorphisms in a small regio...... In summary, we have provided evidence for association between BPD and polymorphisms in a small region of chromosome 12q23-q24 that includes the 30 end of the gene encoding CUX2 and a hypothetical protein, FLJ32356. More...	Positive
CUX2	In summary, we have provided evidence for association between BPD and polymorphisms in a small regio...... In summary, we have provided evidence for association between BPD and polymorphisms in a small region of chromosome 12q23-q24 that includes the 30 end of the gene encoding CUX2 and a hypothetical protein, FLJ32356. More...	Positive

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