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	Lai, T. J.,2005 PMID: 15799788
Citation	Lai, T. J., C. Y. Wu, et al. (2005). Polymorphism screening and haplotype analysis of the tryptophan hydroxylase gene (TPH1) and association with bipolar affective disorder in Taiwan. BMC Med Genet 6: 14.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	108 BPD patients and 103 controls
SNP/Region/Marker Size	10 variants
Predominant Ethnicity	Mongloid
Population	Taiwanese
Gender	The gender ratios are identical in both case and control groups (male to female is 53% to 47 %).
Age Group	Adults : Mean age(SD)(year): 38(13.7) in case and 26.4(7.9) in control groups

Detail Info

Sample Diagnosis	DSM
Sample Status	Since 1998, probands were recruited from bipolar outpatients in the Chung Shan Medical University Hospital and the Taichung Rehabilitation Hospital in Taiwan. Controls were subjects from local volunteer blood donors who have no family or personal history of major affective disorder and other psychiatric disorders were matched to cases on the basis of ethnic or geographic origin, sex, and age.The age of onset is 28.4 (SD=12.7) in all patients and is 30.3(SD=14.5) and 26.4(SD=10.2) in male and female patients, respectively. Clinical interviews were conducted by experienced psychiatrists (leading by Dr. Lai) for all subjects after the study procedure had been fully explained and information on general demographic data, such as age, sex, and ethnicity, was obtained.Patients assessment was purely by direct clinical interview by the treating clinician according the procedure described in the DSM-IV diagnoses of lifetime Major depressive disorder and bipolar I. Additional information required to reach diagnosis was also collected from all clinical and hospital records where available but the comorbidity with other psychiatric/neurological disorders or medical problems were not considered as an inclusion/exclusion criteria. This study was approved by the University Ethics Committee and written informed consent was obtained from all participants. In total, 108 BPD and 103 controls (all Taiwanese Han) were recruited for this study.
Technique	genotyping
Statistical Method	The chi-squared test for allelic and genotypic distributions between patients and controls was performed using the CROSSTAB program implemented by SPSS.All Fisher's exact tests (two tails) and estimation of the odds ratio of BPD associated with a particular haplotype were performed using the PROC FREQ program implemented by SAS package (SAS Institute Inc., Cary, NC, USA).
Result Summary	RESULTS: Haplotype constructions using these 10 SNPs showed that the 3 most common haplotypes in both patients and controls were identical. One of the fourth common haplotype in the patient group (i.e. GGGAGACCCA) was unique and showed a trend of significance with the disease (P = 0.028). However, the significance was abolished after Bonferroni correction thus suggesting the association is weak. In addition, three haplotype-tagged SNPs (htSNPs) were selected to represent all haplotypes with frequencies larger than 2% in the Taiwanese Han population. The defined TPH1 htSNPs significantly reduce the marker number for haplotype analysis thus provides useful information for future association studies in our population. CONCLUSION: Results of this study did not support the role of TPH1 gene in BPD etiology. As the current studies found the TPH1 gene under investigation belongs to the peripheral serotonin system and may link to a cardiac dysfunction phenotype, a second TPH gene that functions predominantly in the brain (i.e., nTPH or TPH2) should be the target for the future association study.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs684302	TPH1	G/A		chi-squared test: genotype, X²=0.46, P-value = 0.793; allele, X²=0.439, P-value = 0.508	No significant association was observed. No significant association was observed.	Negative
rs623580	TPH1	T/A		chi-squared test: genotype, X²=2.17, P-value = 0.304; allele, X²=0.015, P-value = 0.946	No significant association was observed. No significant association was observed.	Negative
rs2237907	TPH1	C/G		chi-squared test: genotype, X²=1.24, P-value = 0.538; allele, X²=0.392, P-value = 0.531	No significant association was observed. No significant association was observed.	Negative
rs211105	TPH1	A/C		chi-squared test: genotype, X²=0.232, P-value = 0.89; allele, X²=0.207, P-value = 0.649	No significant association was observed. No significant association was observed.	Negative
rs2108977	TPH1	C/T		chi-squared test: genotype, X²=3.58, P-value = 0.167; allele, X²=2.13, P-value = 0.144	No significant association was observed. No significant association was observed.	Negative
rs1800532	TPH1	A/C		chi-squared test: genotype, X²=1.726, P-value = 0.422; allele, X²=1.795, P-value = 0.18	No significant association was observed. No significant association was observed.	Negative

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

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
(TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)	G-G-T-A-G-A-C-C-C-A	TPH1	Fisher's Exact Test:global P-value = 0.082, individual P-value = 0.724, OR=0.612, 95%CI=0.14-2.59	No significant association was found . No significant association was found .	Negative
(TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)	G-G-T-T-G-C-C-C-T-A	TPH1	Fisher's Exact Test:global P-value = 0.082, individual P-value = 0.366, OR=1.439, 95%CI=0.70-2.96	No significant association was found . No significant association was found .	Negative
(TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)	G-G-T-T-G-C-C-C-T-G	TPH1	Fisher's Exact Test:global P-value = 0.082, individual P-value = 0.443, OR=2.082, 95%CI=0.38-11.49	No significant association was found . No significant association was found .	Negative
(TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)	T-A-G-A-G-A-C-A-T-G	TPH1	Fisher's Exact Test:global P-value = 0.082, individual P-value = 1, OR=1.031, 95%CI=0.25-4.18	No significant association was found . No significant association was found .	Negative
(TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)	T-A-G-A-G-A-C-C-T-G	TPH1	Fisher's Exact Test:global P-value = 0.082, individual P-value = 1, OR=1.035, 95%CI=0.59-1.80	No significant association was found . No significant association was found .	Negative
(TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)	T-A-G-T-A-A-C-A-C-A	TPH1	Fisher's Exact Test:global P-value = 0.082, individual P-value = 0.105, OR=0.25, 95%CI=0.05-1.19	No significant association was found . No significant association was found .	Negative
(TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)	T-A-G-T-A-A-C-C-T-G	TPH1	Fisher's Exact Test:global P-value = 0.082, individual P-value = 0.058	No significant association was found . No significant association was found .	Negative
(TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)	T-A-G-T-A-A-G-A-C-A	TPH1	Fisher's Exact Test:global P-value = 0.082, individual P-value = 0.755, OR=0.919, 95%CI=0.61-1.38	No significant association was found . No significant association was found .	Negative
(TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)	T-A-G-T-G-C-G-A-C-A	TPH1	Fisher's Exact Test:global P-value = 0.082, individual P-value = 0.498, OR=1.735, 95%CI=0.41-7.36	No significant association was found . No significant association was found .	Negative
(TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)	T-A-G-T-G-A-C-C-T-G	TPH1	Fisher's Exact Test:global P-value = 0.082, individual P-value = 0.443, OR=2.081, 95%CI=0.38-11.49	No significant association was found . No significant association was found .	Negative
(TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)	T-A-G-T-A-A-G-A-T-A	TPH1	Fisher's Exact Test:global P-value = 0.082, individual P-value = 0.278, OR=2.615, 95%CI=0.50-13.64	No significant association was found . No significant association was found .	Negative
(TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)	G-G-G-A-G-A-C-C-C-A	TPH1	Fisher's Exact Test:global P-value = 0.082, individual P-value = 0.028	Significant association was found in individual P-value. Significant association was found in individual P-value.	Positive

Other variants reported by this study for BD (count: 4)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
TPH1 5'flanking T-1721G	TPH1	point mutation	T/G		chi-squared test:genotype, X²=2.79, P-value = 0.248;allele, X²=0.36, P-value = 0.548	No significant association was observed. No significant association was observed.	Negative
TPH1 5'flanking G-347T	TPH1	point mutation	G/T		chi-squared test:genotype, X²=0.048, P-value = 0.976;allele, X²=0.037, P-value = 0.847	No significant association was observed. No significant association was observed.	Negative
TPH1 5'flanking A-1067G	TPH1	point mutation	A/G		chi-squared test:genotype, X²=1.62, P-value = 0.446;allele, X²=0.74, P-value = 0.389	No significant association was observed. No significant association was observed.	Negative
TPH1 3'UTR A27237G	TPH1	point mutation	A/G		chi-squared test:genotype, X²=0.57, P-value = 0.751;allele, X²=0.677, P-value = 0.411	No significant association was observed. No significant association was observed.	Negative

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