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	Lohoff, F. W., 2006 PMID: 16936705
Citation	Lohoff, F. W., J. P. Dahl, et al. (2006). "Variations in the vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) are associated with bipolar i disorder." Neuropsychopharmacology 31(12): 2739-2747.
Disease Type	Bipolar I Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	585 unrelated BPD type I patients and 563 controls
SNP/Region/Marker Size	10 SNPs
Predominant Ethnicity	Caucasian
Population	NIMH collection
Gender	38% male and 62% female patients, 51% male and 49% female controls
Age Group	adults : average age was 41.6 years of patients, 38.5 years of controls

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	Patients were collected at centers involved in the National Institute of Mental Health (NIMH) Genetics Initiative on BPD and carried a diagnosis of BPD type I as defined by DSM-IV criteria. The key criterion for admission of a family to the study was a diagnosis of BPD type I in two or more siblings. Family history information was obtained through the Family Interview for Genetic Studies (FIGS) and medical records were requested. Psychotic symptoms were present in 66% of the probands at some point during their illness. Psychosis was defined as presence of auditory/visual hallucinations and/or paranoid or bizarre delusions.
Technique	genotyping using the ABI 'Assays-on-demand'
Statistical Method	Genotypes and allele frequencies were compared between groups using chi square contingency analysis. A two-tailed type I error rate of 5% was chosen for the analysis. Linkage disequilibrium (LD) and haplotype frequencies were estimated using the COCAPHASE program. The COCAPHASE program uses standard unconditional logistic regression analysis. Correction for multiple testing was performed using permutation correction by the COCAPHASE program.
Result Summary	Allele frequencies differed significantly for the potential functional polymorphism Thr136Ser between BPD patients and controls (p=0.003; df=1; OR=1.34; 95% CI: 1.11-1.62). Polymorphisms in the promoter region (rs988713: p=0.005, df=1; OR=1.31; 95% CI: 1.09-1.59) and intron 8 (rs2279709: p=0.039, df=1; OR=0.84; 95% CI: 0.71-0.99) were also associated with disease. Expression analysis confirmed that VMAT1 is expressed in human brain at the mRNA and protein level. Results suggest that variations in the VMAT1 gene may confer susceptibility to BPD in patients of European descent. Additional studies are necessary to confirm this effect and to elucidate the role of VMAT1 in central nervous system physiology.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs1390938	SLC18A1	Thr/Ile		genotypic P-value = 0.009, allelic P-value = 0.003 for BPI ; genotypic P-value = 0.063, allelic P-value = 0.02 for BP I psychosis	The potential functional polymorphism Thr136Ile in VMAT1 was...... The potential functional polymorphism Thr136Ile in VMAT1 was associated with BPD More...	Positive
rs1497020	SLC18A1	A/G		genotypic P-value = 0.1, allelic P-value = 0.205 for BPI ; genotypic P-value = 0.323, allelic P-value = 0.45 for BP I psychosis		Negative
rs2270637	SLC18A1	Thr/Ser		genotypic P-value = 0.633, allelic P-value = 0.415 for BPI ; genotypic P-value = 0.847, allelic P-value = 0.984 for BP I psychosis		Negative
rs988713	SLC18A1	A/G		genotypic P-value = 0.015, allelic P-value = 0.005 for BPI ; genotypic P-value = 0.085, allelic P-value = 0.029 for BP I psychosis	This SNP is associated with the disease. This SNP is associated with the disease.	Positive
rs3735835	SLC18A1	G/C		genotypic P-value = 0.069, allelic P-value = 0.038 for BPI ; genotypic P-value = 0.1, allelic P-value = 0.035 for BP I psychosis	This SNP is associated with the disease. This SNP is associated with the disease.	Positive
rs2279709	SLC18A1	C/A		genotypic P-value = 0.271, allelic P-value = 0.127 for BPI ; genotypic P-value = 0.322, allelic P-value = 0.159 for BP I psychosis		Negative
rs2270641	SLC18A1	Thr/Pro		genotypic P-value = 0.848, allelic P-value = 0.623 for BPI ; genotypic P-value = 0.642, allelic P-value = 0.356 for BP I psychosis		Negative

Haplotypes reported by this study for BD (count: 5)

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