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	Harvey, M., 2007 PMID: 17167340
Citation	Harvey, M., B. Gagne, et al. (2007). "Polymorphisms in the neuronal isoform of tryptophan hydroxylase 2 are associated with bipolar disorder in French Canadian pedigrees." Psychiatr Genet 17(1): 17-22.
Disease Type	Bipolar Disorder
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	225 BD cases and 221 controls; 485 individuals from 357 nuclear families
SNP/Region/Marker Size	23 SNPs
Predominant Ethnicity	Caucasian
Population	Canadian
Gender	case-control sample: 60% women BPI, 55% women BPII
Age Group	not mentioned

Detail Info

Sample Diagnosis	DSM-IIIR/IV
Sample Status	case-control sample: 191 BPI patients, mean age at onset=28 (SD=11) years, 34 BPII patients, mean age at onset=27 (SD=11) years; family sample: 201 BPI disorder or schizoaffective disorder, BP type (BPI), 64 BPII disorder (BPII), and 79 recurrent major depression (MDD). These pedigrees included 39 affected individuals common to the case group in the case-control study.
Technique	SNPs were genotyped by resequencing of the amplification products.
Statistical Method	Testing for allelic and genotypic association with the BPI and BPII phenotype, as well as the computation of odds ratios and 95% confidence intervals, was tested using CLUMP v1.6. Haplotypes of two to four successive markers were estimated with the expectation maximization algorithm implanted in the cocaphase module of UNPHASE Version 2.40 and with the PHASE program. The family-based association tests were performed using the FBAT software version 1.5.5.
Result Summary	We determined linkage disequilibrium structure in their isolated population and analyzed six tagged single nucleotide polymorphisms in the case-control sample. Whereas no single, single nucleotide polymorphism gave any significant result, a three single nucleotide polymorphism haplotype gave a global P=0.01. Family-based association showed significant association (P=0.004) of one polymorphism (rs4290270) with the major allele overtransmitted to affected offspring. Case-control and family-based association studies further support the presence of a susceptibility locus for bipolar disorder in tryptophan hydroxylase 2 by showing statistically significant associations with both, single nucleotide polymorphism alone and haplotype of single nucleotide polymorphism markers.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs4290270	TPH2	A/T		FBAT P-value = 0.0041, corrected P-value = 0.049, Z=2.866 for T allele under a recessive model, FBAT P-value = 0.4435, Z=-0.766 for A allele, FBAT P-value = 0.3969, Z=-0.847 for AA genotype, FBAT P-value = 0.0702, Z=-1.811 for AT genotype, FBAT P-value = 0.0042, corrected P-value = 0.050, Z=2.860 for TT genotype	Evidence of allelic and genotypic association is found at th...... Evidence of allelic and genotypic association is found at the rs4290270 locus. More...	Positive

Haplotypes reported by this study for BD (count: 7)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs7305115 - rs1007023 - rs4290270	G-T-A	TPH2	cocaphase P-value = 0.222, PHASE P-value = 0.339 in case-control sample; Cocaphase global P-value = 0.018, PHASE global P-value = 0.011	A significantly positive result was observed with the haplot...... A significantly positive result was observed with the haplotype comprising the SNPs rs7305115, rs1007023, and rs4290270 More...	Negative
rs7305115 - rs1007023 - rs4290270	A-T-A	TPH2	cocaphase P-value = 0.16, PHASE P-value = 0.056 in case-control sample; Cocaphase global P-value = 0.018, PHASE global P-value = 0.011	haplotype A-T-A was over-represented in controls haplotype A-T-A was over-represented in controls	Negative
rs7305115 - rs1007023 - rs4290270	A-G-T	TPH2	cocaphase P-value = 0.241, PHASE P-value = 0.172 in case-control sample; Cocaphase global P-value = 0.018, PHASE global P-value = 0.011	A significantly positive result was observed with the haplot...... A significantly positive result was observed with the haplotype comprising the SNPs rs7305115, rs1007023, and rs4290270 More...	Negative
rs7305115 - rs1007023 - rs4290270	G-T-T	TPH2	cocaphase P-value = 0.125, PHASE P-value = 0.063 in case-control sample; Cocaphase global P-value = 0.018, PHASE global P-value = 0.011	A significantly positive result was observed with the haplot...... A significantly positive result was observed with the haplotype comprising the SNPs rs7305115, rs1007023, and rs4290270 More...	Negative
rs1007023 - rs4290270	T-T	TPH2	nominal P-value = 0.0038, Bonferroni corrected P-value = 0.023 under a recessive model	showed a significant excess transmission of the more frequen...... showed a significant excess transmission of the more frequent haplotype, and demonstrated a stronger association between the major allele and BP status More...	Positive
rs7305115 - rs1007023 - rs4290270	A-T-T	TPH2	cocaphase P-value = 0.043, PHASE P-value = 0.03 in case-control sample; Cocaphase global P-value = 0.018, PHASE global P-value = 0.011	haplotype A-T-T was over-represented in cases haplotype A-T-T was over-represented in cases	Positive
rs7305115 - rs1007023 - rs4290270	A-G-A	TPH2	cocaphase P-value = 0.243, PHASE P-value = 0.167 in case-control sample; Cocaphase global P-value = 0.018, PHASE global P-value = 0.011	A significantly positive result was observed with the haplot...... A significantly positive result was observed with the haplotype comprising the SNPs rs7305115, rs1007023, and rs4290270 More...	Negative

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