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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Basic Info

Reference	Xu, C.,2012 PMID: 23277130
Citation	Xu, C., et al. (2012). "Association of the iPLA2beta gene with bipolar disorder and assessment of its interaction with TRPM2 gene polymorphisms." Psychiatr Genet.
Disease Type	Bipolar Disorder
Study Design	case-control and family based
Study Type	Candidate-gene association study
Sample Size	178 White BD patients (128 BD-I and 50 BD-II) and 268 age-matched, sex-matched, and ethnicity-matched healthy individuals for case-control study;296 BD families for family-based study
SNP/Region/Marker Size	3 SNPs
Predominant Ethnicity	Caucasian
Population	American
Gender	the family design, probands (63% women and 37% men)

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	Cases and controls included 178 White BD patients (128 BD-I and 50 BD-II) and 268 age-matched, sex-matched, and ethnicity-matched healthy individuals. Psychiatric diagnoses were confirmed using the SCID-I as described previously (Xu et al., 2006). Healthy individuals assessed by a structured interview with the SCID-I nonpatient version (First et al., 1996) had no personal or family (firstdegree relative) history of psychiatric disorder. For the family design, probands (63% women and 37% men) with a diagnosis of BD-I, BD-II, or schizoaffective disorder, bipolar type, along with their living parents and/or other relatives, from 296 BD families were assessed as described previously (Xu et al., 2009). A lifetime history of psychosis was defined within the context of an episode of mania or depression as extracted from the SCID. The study was approved by the Research Ethics Board of the Centre for Addiction and Mental Health. All participants provided written informed consent.
Technique	Genotyping
Statistical Method	Transmission Disequilibrium Test (TDT) and chi-square tests
Result Summary	The results were analyzed using chi-test and transmission disequilibrium tests, and Haploview. In a secondary analysis, we tested gene-gene interactions between TRPM2 and iPLA2beta on BD vulnerability by logistic regression using a case-only design in PLINK. iPLA2beta-rs3788533 showed a borderline association with BD-I in patients with a history of psychosis in both case-control and family designs. Association with BD as a whole was observed in the family study (significant over transmissions of rs3788533-allele C, P=0.015, PBonferroni=0.03, TDTPHASE). A borderline interaction was found between rs749909 within TRPM2 and rs4375 within iPLA2beta (Puncorrected=0.009), on the basis of the case-only design analyzed with PLINK. A significant association of iPLA2beta variants with BD-I and a trend gene-gene interaction between iPLA2beta and TRPM2 provides additional support for the notion that genetic variation in these two functionally implicated candidates contributes toward the risk and pathophysiology of this illness.

SNPs reported by this study for BD (count: 2)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs3788533	PLA2G6	G/C		Case-control study :BD,OR = 1.01,chi square = 0.01,P-value < 0.05;BD-I,OR = 1.06,chi square = 0.12,P-value < 0.05;BD-II,OR = 0.82,chi square = 0.67,P-value < 0.05;BD-I with a history of psychosis,OR = 1.81,chi square = 4.26,P-value = 0.04;BD-I without a history of psychosis,OR = 0.75,chi square = 1.32,P-value < 0.05;Family based study:BD,309/266(T/UT), P = 0.015,P-Bonferroni = 0.030;BD-I,256/223(T/UT), P = 0.048,P-Bonferroni = 0.096;BD-I probands with history of psychosis,156/130(T/UT), P = 0.115;BD-I probands without history of psychosis,73/57(T/UT), P = 0.070	Association with BD as a whole was observed in the family st...... Association with BD as a whole was observed in the family study. More...	Positive
rs4375	PLA2G6	T/C		Case-control study :BD,OR = 1.18,chi square = 1.41,P-value < 0.05;BD-I,OR = 1.25,chi square = 1.4,P-value < 0.05;BD-II,OR = 0.89,chi square = 0.62,P-value < 0.05;BD-I with a history of psychosis,OR = 0.89,chi square = 0.45,P-value < 0.05;BD-I without a history of psychosis,OR = 1.67,chi square = 4.63,P-value = 0.03;Family based study:Allele T:BD,P > 0.05;BD-I,216/193(T/UT), P = 0.166;BD-I probands with history of psychosis,136/123(T/UT), P = 0.303;BD-I probands without history of psychosis,60/48(T/UT), P = 0.150.	No significant association was observed. No significant association was observed.	Negative

Haplotypes reported by this study for BD (count: 2)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs4375 - rs3788533	C-G	PLA2G6	Family based study: TDT,BD,248/291(T/UT), P = 0.016,P-Bonferroni = 0.03;BD-I,212/247(T/UT), P = 0.038,P-Bonferroni = 0.076;BD-I probands with history of psychosis,120/14(T/UT)8, P = 0.041,P-Bonferroni = 0.082;BD-I probands without history of psychosis,57/69(T/UT), P = 0.133	Association with BD as a whole was observed in the family st...... Association with BD as a whole was observed in the family study More...	Positive
rs4375 - rs3788533	T-C	PLA2G6	Family based study: TDT,BD,260/227(T/UT), P = 0.055	No significant association was observed. No significant association was observed.	Negative

Genes reported by this study for BD (count: 2)

Gene	Statistical Values/Author Comments	Result Category
PLA2G6	Association with BD as a whole was observed in the family study (significant over transmissions of r...... Association with BD as a whole was observed in the family study (significant over transmissions of rs3788533-allele C, P=0.015, PBonferroni=0.03, TDTPHASE). A significant association of iPLA2beta variants with BD-I and a trend gene-gene interaction between iPLA2beta and TRPM2 provides additional support for the notion that genetic variation in these two functionally implicated candidates contributes toward the risk and pathophysiology of this illness. More...	Positive
TRPM2	A borderline interaction was found between rs749909 within TRPM2 and rs4375 within iPLA2beta (Puncor...... A borderline interaction was found between rs749909 within TRPM2 and rs4375 within iPLA2beta (Puncorrected=0.009).A significant association of iPLA2beta variants with BD-I and a trend gene-gene interaction between iPLA2beta and TRPM2 provides additional support for the notion that genetic variation in these two functionally implicated candidates contributes toward the risk and pathophysiology of this illness. More...	Positive

Gene-gene interactions reported by this study for BD (count: 1)

Gene Group	Markers	Statistical Values	Author Comments	Result Category
PLA2G6 TRPM2	rs749909	Interaction: Logistic Regression P-value = 0.009	A borderline interaction was found between rs749909 within T...... A borderline interaction was found between rs749909 within TRPM2 and rs4375 within iPLA2beta. More...	Positive