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	Xu, C.,2009 PMID: 19133961
Citation	Xu, C., P. P. Li, et al. (2009). TRPM2 variants and bipolar disorder risk: confirmation in a family-based association study. Bipolar Disord 11(1): 1-10.
Disease Type	Bipolar Disorder
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	probands from 300 BD families with a diagnosis of BD-I, bipolar disorder type II(BD-II), or schizoaffective disorder-bipolar type
SNP/Region/Marker Size	11 SNPs
Predominant Ethnicity	Caucasian
Population	Canadian
Gender	Female subjects comprised 52% of the sample and 63% of BD probands.
Age Group	Adults : Mean age(SD)(year):35(10)

Detail Info

Sample Diagnosis	DSM and SCID
Sample Status	Probands and family members were assessed by trained interviewers using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), patient edition, and diagnoses were made according to a best estimate procedure.Age at onset of illness, defined as the first distinct episode meeting DSM-IV criteria for depression or hypomania ? mania, was extracted from the SCID-I. BD families were also categorized as those with (43.7%) or without (56.3%) psychotic probands based on lifetime history of psychosis within the context of an episode of mania or depression as extracted from the SCID-I.Almost all probands recruited were outpatients at the time of their participation in the study.Among the 300 families,96.8% were of European, Caucasian origin and included 252 trios (84% of the family sample), 11 extended families, 14 affected sib-pair families, and 23 discordant sib-pair families.
Technique	genotyping
Statistical Method	In the family design, the transmission disequilibrium test (TDT) from the TDTPHASE program of the UNPHASED software, version 2.403 was used.single-marker and haplotype analyses with AAO as a quantitative trait were performed using the FBAT-Wilcoxon test from the Pedigree-Based Association Test[(PBAT), version 3.2 (22)].
Result Summary	RESULTS: The SNP rs1556314 in exon 11 was significantly associated with bipolar disorder type I (BD-I) (p = 0.011, p(permutation) = 0.015) in the case-control dataset and in the family design (p = 0.018, p(permutation) = 0.052, TDTPHASE). Interestingly, the C-T-A haplotype of SNPs rs1618355, rs933151, and rs749909 was significantly associated with early age at onset in BD-I families. CONCLUSION: Significant association of TRPM2 genetic variants with BD in case-control and family datasets further supports a role for TRPM2 in the pathogenesis of this disorder. Overtransmission of the G allele of rs1556314 at exon 11 of TRPM2 in BD-I but not bipolar disorder type II (BD-II) further supports different genetic contributions to the pathogenesis of these bipolar phenotypes.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs933151	TRPM2		C	TDT: in BD families, X²=0.04, P-value = 0.846; in BD-I families, X²=0.01, P-value = 0.935; in BD-II families, X²=0.46, P-value = 0.499	No significant association was observed No significant association was observed	Negative
rs1618355	TRPM2		C	TDT: in BD families, X²=0.2, P-value = 0.653; in BD-I families, X²=0.08, P-value = 0.782; in BD-II families, X²=2.33, P-value = 0.127	No significant association was observed No significant association was observed	Negative
rs1556314	TRPM2		G	TDT: in BD families, X²=1.87, P-value = 0.172; in BD-I families, X²=5.58, P-value = 0.018; in BD-II families, X²=2.76, P-value = 0.097; in BD-I probands (AAO<=24 years), X²=5.04, P-value = 0.024; case-control study: in BD, OR (95% CI)=1.40(1.00-1.96), X²=3.92, P-value = 0.047, P-permutation value=0.056; in BD--I, OR (95% CI)=1.59(1.11-2.28), X²=6.47, P-value = 0.011, P-permutation value=0.015; in BD-II, OR (95% CI)=1.02(0.60-1.73), X²=0, P-value = 0.952, P-permutation value=0.096	Significant association was observed in BD-I probands (AAO<=...... Significant association was observed in BD-I probands (AAO<=24 years)in TDT and in BD-I in the case-control study. More...	Positive
rs749909	TRPM2		G	TDT: in BD families, X²=0.06, P-value = 0.803; in BD-I families, X²=0.38, P-value = 0.536; in BD-II families, X²=0.38, P-value = 0.537	No significant association was observed No significant association was observed	Negative
rs1785437	TRPM2		C	TDT: in BD families, X²=0.06, P-value = 0.812; in BD-I families, X²=0.22, P-value = 0.638; in BD-II families, X²=0.23, P-value = 0.629	No significant association was observed. No significant association was observed.	Negative

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