BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

Search Gene with Disease Search Gene1 with Disease

Study Report

Comment on Study

View All Comments on Study

Basic Info

Reference	Grigoroiu-Serbanescu, M.,2008 PMID: 18797398
Citation	Grigoroiu-Serbanescu, M., C. C. Diaconu, et al. (2008). "Investigation of the tryptophan hydroxylase 2 gene in bipolar I disorder in the Romanian population." Psychiatr Genet 18(5): 240-247.
Disease Type	Bipolar I Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	198 unrelated BPI probands and 180 controls
SNP/Region/Marker Size	16 SNPs
Predominant Ethnicity	Caucasian
Population	Romanian
Gender	The BPI sample consisted of 114 females (57.9%) and 84 males (42.1%).
Age Group	adults : The mean age at interview of the total BPI sample was 41.11 years (SD=13.48)

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	The criterion for inclusion of the patients in the study was to have a history of at least two hospitalized illness episodes (one manic/ mixed and one depressive or two manic episodes). The mean number of hospitalized episodes per patient was 6.49 (SD=4.22, range 2-28).
Technique	Genomic DNA was isolated from whole blood samples using the method of Miller et al. (1988). Genotyping was performed using the MassARRAY system on a Sequenom Compact MALDI-TOF device.
Statistical Method	We determined the power of our sample to detect an association between TPH2 SNPs and BPI disorder using the Genetic Power Calculator. The Hardy-Weinberg equilibrium (HWE) and intermarker linkage disequilibrium as expressed by R² and D' were calculated and visualized using the Haploview v.3.32 software. Single-marker association and haplotype analyses were performed using the program FAMHAP. Single-marker analysis was corrected by permutations in 100 000 simulations for a sample call rate more than or equal to 90%. The genotypic association was computed through a likelihood ratio test based on the expectation maximization algorithm. The null hypothesis that all genotypes have equal odds ratios (ORs) was tested through permutations in 100 000 simulations and correction for multiple testing was undertaken. Haplotype block structure was determined according to the algorithm described by Gabriel et al. Beyond the corrections for multiple testing performed by FAMHAP, we additionally applied the conservative Bonferroni correction for the number of phenotypic traits used in sample subgroups for single SNP and haplotype analysis.
Result Summary	The functional SNP rs17110563 (encoding a Pro206Ser substitution) was present in one Romanian BPI patient and absent in controls. SNPs located in the 5'-region (rs11178997, rs11178998, rs7954758) that had earlier been found to be significantly associated with BPI in a German sample were not associated with BPI in the overall Romanian sample at the single-marker level, but gave evidence for association in a subgroup of patients with paternal transmission of the disease at the haplotypic level. Further evidence of association was identified between haplotypes located in the 3'-region of TPH2 and BPI in the overall sample as well as in the subgroups of familial cases, the patient group with paternal transmission, and the patient group with age of onset below or equal to 25 years.

SNPs reported by this study for BD (count: 15)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs11178997	TPH2	T/A		Cochrane-Armitage trend test P value=0.63		Negative
rs11178998	TPH2	A/G		Cochrane-Armitage trend test P value=0.548		Negative
rs11178999	TPH2	G/A		Cochrane-Armitage trend test P value=0.172		Negative
rs11615016	TPH2	A/G		Cochrane-Armitage trend test P value=0.049; Allelic OR (95% CI)=1.71 (0.99-2.96)		Positive
rs10748185	TPH2	A/G		Cochrane-Armitage trend test P value=0.637		Negative
rs7954758	TPH2	A/G		Cochrane-Armitage trend test P value=0.624		Negative
rs4760820	TPH2	C/G		Cochrane-Armitage trend test P value=0.145		Negative
rs17110563	TPH2	C/T		Cochrane-Armitage trend test P value=0.341		Negative
rs17110477	TPH2	T/A		Cochrane-Armitage trend test P value=0.126		Negative
rs1843809	TPH2	T/G		Cochrane-Armitage trend test P value=0.462		Negative
rs17722134	TPH2	A/G		Cochrane-Armitage trend test P value=0.055; Allelic OR (95% CI)=3.69 (1.03-13.19)		Negative
rs1386486	TPH2	C/T		Cochrane-Armitage trend test P value=0.847		Negative
rs11834097	TPH2	C/T		Cochrane-Armitage trend test P value=0.214		Negative
rs1487275	TPH2	T/G		Cochrane-Armitage trend test P value=0.537		Negative
rs1386497	TPH2	A/C		Cochrane-Armitage trend test P value=0.68		Negative

Haplotypes reported by this study for BD (count: 6)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs1386497 - rs11834097 - rs4760820 - rs17722134	CCCA	TPH2	OR=1.05		Negative
rs1386497 - rs11834097 - rs4760820 - rs17722134	ATCA	TPH2	OR=0.8		Negative
rs1386497 - rs11834097 - rs4760820 - rs17722134	ACGA	TPH2	OR=0.79		Negative
rs1386497 - rs11834097 - rs4760820 - rs17722134	ACCA	TPH2	OR=1.93	The ORs and frequencies in cases and controls indicate that ...... The ORs and frequencies in cases and controls indicate that the haplotypes ACCA and ACCG are associated with the BPI disorder. More...	Positive
rs1386497 - rs11834097 - rs4760820 - rs17722134	ACCG	TPH2	OR=3.35	The ORs and frequencies in cases and controls indicate that ...... The ORs and frequencies in cases and controls indicate that the haplotypes ACCA and ACCG are associated with the BPI disorder. More...	Positive
rs1386497 - rs11834097 - rs4760820 - rs17722134		TPH2	P value for the global X<sup>2</sup>=0.0096	This haplotype was significant in the total sample This haplotype was significant in the total sample	Positive

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