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., 2013 PMID: 23337945
Citation	Lohoff, F. W., et al. (2013). "Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing." Mol Psychiatry.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study, Rare variant study
Sample Size	196 BPD individuals for all VMAT1 exons, 390 BPD and 196 Caucasian controls were sequenced for exons 2 and 3; 4023 BPD patients and 3305 controlsfrom the NIMH Genetic Initiative for genotyping
SNP/Region/Marker Size	5 variants
Predominant Ethnicity	Caucasian

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	DNA samples from BPD type I patients for sequencing, as diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, were obtained from the NIMH Genetics Initiative on BPD. BPD patients (n=4023) and normal controls (n=3305) of European descent for genotyping were from the NIMH Genetic Initiative.
Technique	The VMAT1 gene exons and exon-intron boundaries were sequenced using exon-specific primers; Genotyping of the functional rare variants Phe84Ser (rs17215801) and Arg138Leu (rs148468662) was performed by using standard ABI TaqMan genotyping protocols. Genotyping of the common variants Thr4Pro (rs2270641), Ser98Thr (rs2270637) and Thr136Ile (rs1390938) in the human imaging data set (see above) was carried out using standard TaqMan genotyping protocols, unless otherwise noted (ABI assays were Thr4Pro: C_22271506_10; Ser98Thr: C_2716008_1_; and Thr136Ile: C_8804621_1_).
Statistical Method	Fisher exact test
Result Summary	Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits and risk for psychopathology.Molecular Psychiatry advance online publication, 22 January 2013; doi:10.1038/mp.2012.193.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs150204882	SLC18A1			no P-value	DNA Sanger sequencing of BPD patients identified several nov...... DNA Sanger sequencing of BPD patients identified several novel and rare variants. More...	Trend
rs17215801	SLC18A1			P-value=0.009	DNA Sanger sequencing of BPD patients identified several nov...... DNA Sanger sequencing of BPD patients identified several novel and rare variants. The Ser84 allele was absent in controls but present in seven BPD individuals, including one homozygote and six heterozygotes. More...	Positive
rs17222218	SLC18A1			no P-value	DNA Sanger sequencing of BPD patients identified several nov...... DNA Sanger sequencing of BPD patients identified several novel and rare variants. More...	Trend
rs148468662	SLC18A1			P-value=0.199	DNA Sanger sequencing of BPD patients identified several nov...... DNA Sanger sequencing of BPD patients identified several novel and rare variants. The Leu138 frequency did not differ statistically between cases and controls. More...	Negative
rs17222183	SLC18A1			no P-value	DNA Sanger sequencing of BPD patients identified several nov...... DNA Sanger sequencing of BPD patients identified several novel and rare variants. More...	Trend

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