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	Lopez, V. A., 2007 PMID: 16806105
Citation	Lopez, V. A., S. Detera-Wadleigh, et al. (2007). "Nested association between genetic variation in tryptophan hydroxylase II, bipolar affective disorder, and suicide attempts." Biol Psychiatry 61(2): 181-186.
Disease Type	Bipolar Disorder
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	613 individuals in 203 nuclear families
SNP/Region/Marker Size	4 SNPs
Predominant Ethnicity
Population	NIMH collections: waves 1-4
Gender	64% female
Age Group	not mentioned

Detail Info

Sample Diagnosis	DSM-III/IV criteria
Sample Status	Most of the sample (almost 60%) consists of subjects with BPI, but bipolar II and recurrent major depressive disorder occur commonly among their relatives. Schizoaffective disorder was diagnosed in 53 individuals (2.3%). Completed suicides were not ascertained, but 548 individuals in 385 families (27%) reported a history of one or more SA.
Replication Size	1405 individuals in 467 nuclear families
Technique	genotyping, the PCR primers and the internal sequencing primers were designed by using 'PSQ Assay Design' from Pyrosequencing software.
Statistical Method	Family-based association analysis was performed with two well-established statistical tools. Effect sizes were estimated with TDTPHASE version 2.401. Power was estimated with the Genetic Power Calculator.
Result Summary	Single-marker analysis failed to detect significant genetic association with BPAD or SA, but the number of informative families was small. Haplotype analysis showed significant association with both BPAD and SA, and the same haplotype was significantly associated with both BPAD and SA in a replication sample. Case-only analysis, stratified by SA, suggested that TPH2 was not an independent genetic risk factor for SA in this sample. The TPH2 might contribute to the risk of both BPAD and SA in families with BPAD. Further studies are needed to uncover the functional genetic variation that accounts for the observed associations.

SNPs reported by this study for BD (count: 4)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs9325202	TPH2	A/G		FBAT P-value = 0.634, Z=0.475 in the NIMH 'Wave 3' Sample	did not show significant association with BPAD or with SA in...... did not show significant association with BPAD or with SA in the individual marker tests More...	Negative
rs1386494	TPH2	A/G		FBAT P-value = 0.106, Z=-1.616 in the NIMH 'Wave 3' Sample	did not show significant association with BPAD or with SA in...... did not show significant association with BPAD or with SA in the individual marker tests More...	Negative
rs11178997	TPH2	A/T		FBAT P-value = 0.511, Z=0.656 in the NIMH 'Wave 3' Sample	did not show significant association with BPAD or with SA in...... did not show significant association with BPAD or with SA in the individual marker tests More...	Negative
rs1007023	TPH2	G/T		FBAT P-value = 0.055, Z=-1.916 in the NIMH 'Wave 3' Sample	this marker displayed association with BPAD at the p=0.0553 ...... this marker displayed association with BPAD at the p=0.0553 level of significance, although it was informative in only 42 families. More...	Negative

Haplotypes reported by this study for BD (count: 3)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs1386494 - rs1007023 - rs9325202	A-G-A	TPH2	FBAT P-value = 0.087, Z=-1.708, global P-value = 0.0396, X<sup>2</sup>(4)=10.051 in the NIMH 'Wave 3' Sample; FBAT P-value = 0.63, Z=-0.479, global P-value = 0.04 in the replication sample; FBAT global P-value = 0.0124 in the total sample	Three-marker haplotype tests revealed significant global ass...... Three-marker haplotype tests revealed significant global association with BPAD in the NIMH 'Wave 3' Sample; FBAT again detected significant global association with BPAD in the total sample More...	Negative
rs1386494 - rs1007023 - rs9325202	G-T-A	TPH2	FBAT P-value = 0.034, Z=2.12, global P-value = 0.0396, X<sup>2</sup>(4)=10.051 in the NIMH 'Wave 3' Sample; FBAT P-value = 0.04, Z=2.012, global P-value = 0.04 in the replication sample; TDTPHASE OR=1.07, 95% CI=0.865-1.138 for G-T-A haplotype; FBAT global P-value = 0.0124 in the total sample	Three-marker haplotype tests revealed significant global ass...... Three-marker haplotype tests revealed significant global association with BPAD in the NIMH 'Wave 3' Sample; the over-transmitted haplotype that contributed to this association was predominantly G-T-A; there was significant overtransmission of the G-T-A haplotype to offspring with BPAD in the replication test; FBAT again detected significant global association with BPAD in the total sample More...	Positive
rs1386494 - rs1007023 - rs9325202	G-T-G	TPH2	FBAT P-value = 0.983, Z=0.02, global P-value = 0.0396, X<sup>2</sup>(4)=10.051 in the NIMH 'Wave 3' Sample; FBAT P-value = 0.21, Z=-1.236, global P-value = 0.04 in the replication sample; FBAT global P-value = 0.0124 in the total sample	Three-marker haplotype tests revealed significant global ass...... Three-marker haplotype tests revealed significant global association with BPAD in the NIMH 'Wave 3' Sample; FBAT again detected significant global association with BPAD in the total sample More...	Negative

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