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., 2006 PMID: 16252251
Citation	Xu, C., F. Macciardi, et al. (2006). "Association of the putative susceptibility gene, transient receptor potential protein melastatin type 2, with bipolar disorder." Am J Med Genet B Neuropsychiatr Genet 141B(1): 36-43.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	124 BD-I patients, 54 BD-II patients and 268 controls
Predominant Ethnicity	Caucasian
Population	British Isles, European-Other, Recent admixture of Europeans and Uncertain European ancestry
Gender	36 female and 18 male BD-II, 82 female and 42 male BD-I, 159 female and 109 male controls
Age Group	adults : mean age=35.5 (SD=8.9) years of BD-II, mean age=37.9 (SD=10.9) years of BD-I, mean age=38.7 (SD=9.1) years of controls

Detail Info

Sample Diagnosis	Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I)
Sample Status	Age of onset was significantly lower in BD-II (16.5, s.d. 6.0 years) compared with BD-I patients (20.4, s.d. 8.2 years; t=3.05, df=171, P=0.003).
Technique	genotyping was performed using the 5' nuclease allelic discrimination TaqMan assay in a 96-well format
Statistical Method	Association between the haplotypes and diagnostic groups was tested using COCAPHASE within the UNPHASED suite of programs, as well as PowerMarker3, which obviates the effects of multiple testing. Disease association of individual SNP allele, genotype or haplotype frequencies with BD patients, as a group, compared with healthy individuals, was assessed using 22 or 23 contingency tables, two-tailed chi square tests, or Fisher exact tests. Differences with two-tailed probability values of P<0.05 were taken as statistically significant. P-values for tests of allelic and genotype association were conservatively corrected for multiple testing using the Bonferroni method.
Result Summary	SNP rs1618355 in intron 18 was significantly associated with BD as a whole (P < 7.0 x 10(-5); odds ratio (OR) = 2.60), and when stratified into BD-I (P < 7.0 x 10(-5), OR = 2.48) and BD-II (P = 7.0 x 10(-5), OR = 2.88) subgroups. In addition, the alleles of the individual SNPs forming a seven marker at-risk haplotype were in excess in BD (12.0% in BD vs. 0.9% in controls; P = 2.3 x 10(-12)). A weak relationship was also detected between BLCL [Ca(2+)](B) and TRPM2 SNP rs1612472 in intron 19. These findings suggest genetic variants of the TRPM2 gene increase risk for BD and support the notion that TRPM2 may be involved in the pathophysiology of BD.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs2838556	TRPM2	T/C		allelic P-value = 0.119, X²=2.43, genotypic P-value = 0.194, X²=3.28 in BD; allelic P-value = 0.023, X²=5.18, genotypic P-value = 0.057, X²=5.74 in BD-I ; allelic P-value = 0.602, X²=0.27, genotypic P-value = 0.702, X²=0.71 in BD-II		Positive
rs734336	TRPM2	T/C		allelic P-value = 0.119, X²=2.43, genotypic P-value = 0.292, X²=2.46 in BD; allelic P-value = 0.015, X²=5.88, genotypic P-value = 0.046, X²=6.14 in BD-I ; allelic P-value = 0.42, X²=0.65, genotypic P-value = 0.624, X²=0.94 in BD-II		Positive
rs749909	TRPM2	A/G		allelic P-value = 0.013, X²=6.19, genotypic P-value = 0.02, X²=7.85 in BD; allelic P-value = 0.019, X²=5.48, genotypic P-value = 0.008, X²=9.74 in BD-I ; allelic P-value = 0.151, X²=2.07, genotypic P-value = 0.188, X²=3.35 in BD-II		Positive
rs933151	TRPM2	T/C		allelic P-value = 0.002, corrected P-value = 0.011, X²=10.13, genotypic P-value = 0.003, corrected P-value = 0.063, X²=11.47 in BD; allelic P-value = 0.008, corrected P-value = 0.055, X²=7.09, genotypic P-value = 0.02, X²=7.8 in BD-I; allelic P-value = 0.014, X²=6.11, genotypic P-value = 0.003, corrected P-value = 0.042, X²=11.97 in BD-II		Positive
rs1612472	TRPM2	T/C		allelic P-value = 0.00003, corrected P-value = 0.00022, X²=17.31, genotypic P-value = 3.2E-03, corrected P-value = 7.0E-03 , X²=16.12 in BD; allelic P-value = 0.0013, corrected P-value = 0.009, X²=10.36, genotypic P-value = 6.0E-03, X²=10.19 in BD-I; allelic P-value = 0.00023, corrected P-value = 0.0016, X²=13.61, genotypic P-value = 4.3E-03, corrected P-value = 7.0E-03 , X²=15.52 in BD-II	Statistically significant increased allele 2 (minor allele) ...... Statistically significant increased allele 2 (minor allele) frequencies were observed for intron 18 and 19 SNPs in BD as compared with those in healthy controls. Moreover, the allele 2 frequencies of intron 18 and intron 19 SNPs were also significantly increased in both BD-I and BD-II patient groups as compared with controls. More...	Positive
rs1618355	TRPM2	A/C		allelic P-value < 0.00001, corrected P-value < 7.0E-5 , X²=41.77, genotypic P-value = 1.20E-09, corrected P-value = 2.0E-08, X²=41.05 in BD; allelic P-value < 0.00001, corrected P-value < 7.0E-05 , X²=30.97, genotypic P-value = 1.5E-07, corrected P-value = 3.0E-06, X²=31.44 in BD-I; allelic P-value = 0.00001, corrected P-value < 7.0E-05 , X²=24.45, genotypic P-value = 2.6E-07, corrected P-value = 3.6E-06 , X²=30.35 in BD-II	Statistically significant increased allele 2 (minor allele) ...... Statistically significant increased allele 2 (minor allele) frequencies were observed for intron 18 and 19 SNPs in BD as compared with those in healthy controls. Moreover, the allele 2 frequencies of intron 18 and intron 19 SNPs were also significantly increased in both BD-I and BD-II patient groups as compared with controls. More...	Positive
rs1785437	TRPM2	T/C		allelic P-value = 0.006, corrected P-value = 0.042, X²=7.43, genotypic P-value = 0.017, X²=8.2 in BD; allelic P-value = 0.019, X²=5.48, genotypic P-value = 0.043, X²=6.3 in BD-I ; allelic P-value = 0.045, X²=4.01, genotypic P-value = 0.037, X²=6.6 in BD-II		Positive

Haplotypes reported by this study for BD (count: 8)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs734336 - rs2838556 - rs1785437 - rs1618355 - rs1612472 - rs933151 - rs749909	T-T-T-A-T-T-A	TRPM2	COCAPHASE P-value = 5.6E-15 , X<sup>2</sup>=61.04; Global P-value of 1.5E-17 (1.05E-16 after correcting for multiple testing)		Positive
rs734336 - rs2838556 - rs1785437 - rs1618355 - rs1612472 - rs933151 - rs749909	T-T-T-A-T-T-G	TRPM2	COCAPHASE P-value = 0.206, X<sup>2</sup>=1.6; Global P-value of 1.5E-17 (1.05E-16 after correcting for multiple testing)		Negative
rs734336 - rs2838556 - rs1785437 - rs1618355 - rs1612472 - rs933151 - rs749909	T-T-C-C-C-C-G	TRPM2	COCAPHASE P-value = 0.538, X<sup>2</sup>=0.38; Global P-value of 1.5E-17 (1.05E-16 after correcting for multiple testing)		Negative
rs734336 - rs2838556 - rs1785437 - rs1618355 - rs1612472 - rs933151 - rs749909	T-T-T-A-C-T-A	TRPM2	COCAPHASE P-value = 0.047, X<sup>2</sup>=3.94; Global P-value of 1.5E-17 (1.05E-16 after correcting for multiple testing)	A number of susceptible haplotypes were detected A number of susceptible haplotypes were detected	Positive
rs734336 - rs2838556 - rs1785437 - rs1618355 - rs1612472 - rs933151 - rs749909	T-T-C-C-C-C-A	TRPM2	COCAPHASE P-value = 0.61, X<sup>2</sup>=0.26; Global P-value of 1.5E-17 (1.05E-16 after correcting for multiple testing)		Negative
rs734336 - rs2838556 - rs1785437 - rs1618355 - rs1612472 - rs933151 - rs749909	T-T-T-C-T-T-G	TRPM2	COCAPHASE P-value = 1.5E-03 , X<sup>2</sup>=14.39; Global P-value of 1.5E-17 (1.05E-16 after correcting for multiple testing)	A number of susceptible haplotypes were detected A number of susceptible haplotypes were detected	Positive
rs734336 - rs2838556 - rs1785437 - rs1618355 - rs1612472 - rs933151 - rs749909	C-C-C-G-C-C-A	TRPM2	COCAPHASE P-value = 0.01, X<sup>2</sup>=6.57; Global P-value of 1.5E-17 (1.05E-16 after correcting for multiple testing)	A number of susceptible haplotypes were detected A number of susceptible haplotypes were detected	Positive
rs734336 - rs2838556 - rs1785437 - rs1618355 - rs1612472 - rs933151 - rs749909	T-T-T-C-T-T-A	TRPM2	COCAPHASE P-value = 2.3E-12, X<sup>2</sup>=49.24; Global P-value of 1.5E-17 (1.05E-16 after correcting for multiple testing)	A number of susceptible haplotypes were detected: the T-T-T-...... A number of susceptible haplotypes were detected: the T-T-T-C-T-T-A haplotype is one among these showing greatest statistical significance with a frequency of 12.0% in the BD cohort and 0.9% in controls. More...	Positive

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