Study Report

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Basic Info

Reference	Barden, N., 2006 PMID: 16673375
Citation	Barden, N., M. Harvey, et al. (2006). "Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder." Am J Med Genet B Neuropsychiatr Genet 141B(4): 374-382.
Disease Type	Bipolar Disorder
Study Design	case-control and family-based
Study Type	Mutation study and candidate-gene association study
Sample Size	Pedigrees: 485 individuals from 41 families; Case/control sample: 213 unrelated patients and 214 controls
SNP/Region/Marker Size	24 SNPs
Predominant Ethnicity
Population	Canadian
Gender	60% female of BPI patients, 55% female of BP II patients

Detail Info

Sample Diagnosis	French translation of the Structured Clinical Interview for DSM-IIIR/IV
Sample Status	Pedigrees: 485 individuals from 41 families of the SLSJ region of Quebec were ascertained, including 105 bipolar I disorder or schizoaffective disorder, bipolar type (BPI), 42 bipolar II disorder (BPII), 54 recurrent major depression (MDD) and 57 single episode major depression. Case/control sample: The SLSJ case sample was composed of 213 unrelated individuals with attachments to the founding population of SLSJ and included BPI (n=182, mean age at onset=28, SD=11), and BP II (n=31, mean age at onset=27, SD=11) diagnosed subjects.
Technique	direct sequencing and genotyping by resequencing of the amplification products
Statistical Method	Testing for allelic and genotypic association with the BPI or BPII phenotype, as well as the computation of odds ratios and 95% confidence intervals, was tested with the Fisher's exact test from the SISA webserver. Haplotypes, either within block or inter-block, were estimated with the expectation-maximization (EM) algorithm implanted in the cocaphase module of UNPHASE Version 2.40. The family-based association tests were done using the FBAT software version 1.5.5.
Result Summary	Allelic, genotypic or family-based association studies suggest the presence of two susceptibility loci, the P2RX7 and CaMKK2 genes. The strongest association was observed in bipolar families at the non-synonymous SNP P2RX7-E13A (rs2230912, P-value=0.000708), which results from an over-transmission of the mutant G-allele to affected offspring. This Gln460Arg polymorphism occurs at an amino acid that is conserved between humans and rodents and is located in the C-terminal domain of the P2X7 receptor, known to be essential for normal P2RX7 function.

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

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs504677	P2RX7	C/T	Allelic P-value = 0.387, OR (CI 95%)=0.88 (0.66-1.17), genotypic P-value = 0.0262, OR (CI 95%)=0.5 (0.27-0.92) under a recessive model	It gave significant allelic and/or genotypic association und...... It gave significant allelic and/or genotypic association under additive, dominant and recessive models. More...	Positive
rs3817190	CAMKK2	A/T	FBAT P-value = 0.01548, Z=2.421 for allelic analysis under an additive model; FBAT P-value = 0.04846, Z=1.973 for A/A; FBAT P-value = 0.79963, Z=-0.254 for A/T; FBAT P-value = 0.12131, Z=-1.549 for T/T	It showed significant associations (P-value <0.05). We obser...... It showed significant associations (P-value <0.05). We observed the positively associated polymorphism, CAMKK2-E01B with the additive model. More...	Positive
rs1718119	P2RX7	G/A	Allelic P-value = 0.9343, OR (CI 95%)=1.02 (0.77-1.35), genotypic P-value = 0.0172, OR (CI 95%)=1.34 (0.90-1.98) under an additive model	It gave significant allelic and/or genotypic association und...... It gave significant allelic and/or genotypic association under additive, dominant and recessive models. More...	Positive
rs2230912	P2RX7	A/G	FBAT P-value = 0.000708, Z=3.387 for allelic analysis under an additive model; FBAT P-value = 0.04253, Z=-2.028 for A/A; FBAT P-value = 0.4917, Z=0.688 for A/G; FBAT P-value = 0.00156, Z=3.157 for G/G	It showed significant associations (P-value <0.05). We obser...... It showed significant associations (P-value <0.05). We observed the positively associated polymorphism, P2RX7-E13A with the additive model. More...	Positive
rs1653625	P2RX7	C/G	Allelic P-value = 0.018, OR (CI 95%)=1.43 (1.07-1.92), genotypic P-value = 0.008, OR (CI 95%)=1.7 (1.16-2.51) under a dominant model	It gave significant allelic and/or genotypic association und...... It gave significant allelic and/or genotypic association under additive, dominant and recessive models. More...	Positive

Haplotypes reported by this study for BD (count: 33)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs1653625 - rs28360463 - rs1653622 - rs11065500 - rs11065501 - rs4980999 - rs3817190	A-C-A-A-G-C-A	P2RX7 CAMKK2	chi-square P-value = 0.106, LRS (global P-value)=0.0249 with a sliding window strategy	The other 7-SNP positively associated window bordered by mar...... The other 7-SNP positively associated window bordered by markers P2RX7-UTR3A and CAMKK2-E01B comprises blocks 3 and 4 and the associated marker P2RX4-UTR3A. More...	Negative
rs1653625 - rs28360463 - rs1653622 - rs11065500 - rs11065501 - rs4980999 - rs3817190	A-C-A-A-C-T-T	P2RX7 CAMKK2	chi-square P-value = 0.544, LRS (global P-value)=0.0249 with a sliding window strategy	The other 7-SNP positively associated window bordered by mar...... The other 7-SNP positively associated window bordered by markers P2RX7-UTR3A and CAMKK2-E01B comprises blocks 3 and 4 and the associated marker P2RX4-UTR3A. More...	Negative
rs1653625 - rs28360463 - rs1653622 - rs11065500 - rs11065501 - rs4980999 - rs3817190	A-C-A-A-C-C-T	P2RX7 CAMKK2	chi-square P-value = 0.487, LRS (global P-value)=0.0249 with a sliding window strategy	The other 7-SNP positively associated window bordered by mar...... The other 7-SNP positively associated window bordered by markers P2RX7-UTR3A and CAMKK2-E01B comprises blocks 3 and 4 and the associated marker P2RX4-UTR3A. More...	Negative
rs1653625 - rs28360463 - rs1653622 - rs11065500 - rs11065501 - rs4980999 - rs3817190	A-C-A-A-C-C-A	P2RX7 CAMKK2	chi-square P-value = 0.685, LRS (global P-value)=0.0249 with a sliding window strategy	The other 7-SNP positively associated window bordered by mar...... The other 7-SNP positively associated window bordered by markers P2RX7-UTR3A and CAMKK2-E01B comprises blocks 3 and 4 and the associated marker P2RX4-UTR3A. More...	Negative
rs1653625 - rs28360463 - rs1653622 - rs11065500 - rs11065501 - rs4980999 - rs3817190	A-A-G-G-C-T-T	P2RX7 CAMKK2	chi-square P-value = 0.362, LRS (global P-value)=0.0249 with a sliding window strategy	The other 7-SNP positively associated window bordered by mar...... The other 7-SNP positively associated window bordered by markers P2RX7-UTR3A and CAMKK2-E01B comprises blocks 3 and 4 and the associated marker P2RX4-UTR3A. More...	Negative
rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912 - rs3751144 - rs3751143 - rs1653625	T-G-G-C-A-C-A-C	P2RX7	chi-square P-value = 0.133, LRS (global P-value)=0.041	We identified global significant P-values for blocks 2 with ...... We identified global significant P-values for blocks 2 with P-value = 0.0410. The haplotype block 2 defines the last six exons of the P2RX7 gene, hence supporting the prior single marker analysis. More...	Negative
rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912 - rs3751144 - rs3751143 - rs1653625	C-A-G-C-G-C-A-C	P2RX7	chi-square P-value = 0.012, LRS (global P-value)=0.041	We identified global significant P-values for blocks 2 with ...... We identified global significant P-values for blocks 2 with P-value = 0.0410. The haplotype block 2 defines the last six exons of the P2RX7 gene, hence supporting the prior single marker analysis. More...	Positive
rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912 - rs3751144 - rs3751143 - rs1653625	C-G-A-C-A-C-A-A	P2RX7	chi-square P-value = 0.101, LRS (global P-value)=0.041	We identified global significant P-values for blocks 2 with ...... We identified global significant P-values for blocks 2 with P-value = 0.0410. The haplotype block 2 defines the last six exons of the P2RX7 gene, hence supporting the prior single marker analysis. More...	Negative
rs1653625 - rs28360463 - rs1653622 - rs11065500 - rs11065501 - rs4980999 - rs3817190	C-C-A-A-C-C-T	P2RX7 CAMKK2	chi-square P-value = 0.012, LRS (global P-value)=0.0249 with a sliding window strategy	The other 7-SNP positively associated window bordered by mar...... The other 7-SNP positively associated window bordered by markers P2RX7-UTR3A and CAMKK2-E01B comprises blocks 3 and 4 and the associated marker P2RX4-UTR3A. More...	Positive
rs1653625 - rs28360463 - rs1653622 - rs11065500 - rs11065501 - rs4980999 - rs3817190	A-C-G-A-C-C-T	P2RX7 CAMKK2	chi-square P-value = 0.327, LRS (global P-value)=0.0249 with a sliding window strategy	The other 7-SNP positively associated window bordered by mar...... The other 7-SNP positively associated window bordered by markers P2RX7-UTR3A and CAMKK2-E01B comprises blocks 3 and 4 and the associated marker P2RX4-UTR3A. More...	Negative
rs1653625 - rs28360463 - rs1653622 - rs11065500 - rs11065501 - rs4980999 - rs3817190	A-C-G-A-C-C-A	P2RX7 CAMKK2	chi-square P-value = 0.163, LRS (global P-value)=0.0249 with a sliding window strategy	The other 7-SNP positively associated window bordered by mar...... The other 7-SNP positively associated window bordered by markers P2RX7-UTR3A and CAMKK2-E01B comprises blocks 3 and 4 and the associated marker P2RX4-UTR3A. More...	Negative
rs1653625 - rs28360463 - rs1653622 - rs11065500 - rs11065501 - rs4980999 - rs3817190	A-C-A-A-G-C-T	P2RX7 CAMKK2	chi-square P-value = 0.073, LRS (global P-value)=0.0249 with a sliding window strategy	The other 7-SNP positively associated window bordered by mar...... The other 7-SNP positively associated window bordered by markers P2RX7-UTR3A and CAMKK2-E01B comprises blocks 3 and 4 and the associated marker P2RX4-UTR3A. More...	Negative
rs208293 - rs208294 - rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912	C-T-T-G-A-C-G	P2RX7	chi-square P-value = 0.824, LRS (global P-value)=0.0178 with a sliding window strategy	The 7-SNP positively associated haplotype window bordered by...... The 7-SNP positively associated haplotype window bordered by P2RX7-I04B and P2RX7-E13A overlaps blocks 1 and 2 and is characterized by a haplotype strictly observed in the case group (P-value = 0.0006) bearing the mutated allele for the non-synonymous SNP P2RX7-E08A. More...	Negative
rs208293 - rs208294 - rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912	T-C-C-A-G-C-A	P2RX7	chi-square P-value = 0.0006, LRS (global P-value)=0.0178 with a sliding window strategy	The 7-SNP positively associated haplotype window bordered by...... The 7-SNP positively associated haplotype window bordered by P2RX7-I04B and P2RX7-E13A overlaps blocks 1 and 2 and is characterized by a haplotype strictly observed in the case group (P-value = 0.0006) bearing the mutated allele for the non-synonymous SNP P2RX7-E08A. More...	Positive
rs208293 - rs208294 - rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912	C-T-C-G-G-C-A	P2RX7	chi-square P-value = 0.959, LRS (global P-value)=0.0178 with a sliding window strategy	The 7-SNP positively associated haplotype window bordered by...... The 7-SNP positively associated haplotype window bordered by P2RX7-I04B and P2RX7-E13A overlaps blocks 1 and 2 and is characterized by a haplotype strictly observed in the case group (P-value = 0.0006) bearing the mutated allele for the non-synonymous SNP P2RX7-E08A. More...	Negative
rs208293 - rs208294 - rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912	C-T-C-G-G-G-A	P2RX7	chi-square P-value = 0.391, LRS (global P-value)=0.0178 with a sliding window strategy	The 7-SNP positively associated haplotype window bordered by...... The 7-SNP positively associated haplotype window bordered by P2RX7-I04B and P2RX7-E13A overlaps blocks 1 and 2 and is characterized by a haplotype strictly observed in the case group (P-value = 0.0006) bearing the mutated allele for the non-synonymous SNP P2RX7-E08A. More...	Negative
rs208293 - rs208294 - rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912	C-C-C-G-G-C-A	P2RX7	chi-square P-value = 0.864, LRS (global P-value)=0.0178 with a sliding window strategy	The 7-SNP positively associated haplotype window bordered by...... The 7-SNP positively associated haplotype window bordered by P2RX7-I04B and P2RX7-E13A overlaps blocks 1 and 2 and is characterized by a haplotype strictly observed in the case group (P-value = 0.0006) bearing the mutated allele for the non-synonymous SNP P2RX7-E08A. More...	Negative
rs208293 - rs208294 - rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912	C-T-C-A-G-C-A	P2RX7	chi-square P-value = 0.911, LRS (global P-value)=0.0178 with a sliding window strategy	The 7-SNP positively associated haplotype window bordered by...... The 7-SNP positively associated haplotype window bordered by P2RX7-I04B and P2RX7-E13A overlaps blocks 1 and 2 and is characterized by a haplotype strictly observed in the case group (P-value = 0.0006) bearing the mutated allele for the non-synonymous SNP P2RX7-E08A. More...	Negative
rs1653625 - rs4980999 - rs3817190 - rs28360477	G-C-A-C	P2RX4 CAMKK2	chi-square P-value = 0.411, LRS (global P-value)=0.039	We identified global significant P-values for blocks 4 with ...... We identified global significant P-values for blocks 4 with P-value = 0.0390. The haplotype block 4 encloses the associated SNP P2RX4-UTR3A, hence supporting the prior single marker analysis. More...	Negative
rs208293 - rs208294 - rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912	C-C-C-A-G-C-A	P2RX7	chi-square P-value = 0.523, LRS (global P-value)=0.0178 with a sliding window strategy	The 7-SNP positively associated haplotype window bordered by...... The 7-SNP positively associated haplotype window bordered by P2RX7-I04B and P2RX7-E13A overlaps blocks 1 and 2 and is characterized by a haplotype strictly observed in the case group (P-value = 0.0006) bearing the mutated allele for the non-synonymous SNP P2RX7-E08A. More...	Negative
rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912 - rs3751144 - rs3751143 - rs1653625	C-G-G-G-A-T-A-A	P2RX7	chi-square P-value = 0.346, LRS (global P-value)=0.041	We identified global significant P-values for blocks 2 with ...... We identified global significant P-values for blocks 2 with P-value = 0.0410. The haplotype block 2 defines the last six exons of the P2RX7 gene, hence supporting the prior single marker analysis. More...	Negative
rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912 - rs3751144 - rs3751143 - rs1653625	C-G-G-C-A-C-A-C	P2RX7	chi-square P-value = 0.249, LRS (global P-value)=0.041	We identified global significant P-values for blocks 2 with ...... We identified global significant P-values for blocks 2 with P-value = 0.0410. The haplotype block 2 defines the last six exons of the P2RX7 gene, hence supporting the prior single marker analysis. More...	Negative
rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912 - rs3751144 - rs3751143 - rs1653625	T-G-A-C-G-C-A-A	P2RX7	chi-square P-value = 0.551, LRS (global P-value)=0.041	We identified global significant P-values for blocks 2 with ...... We identified global significant P-values for blocks 2 with P-value = 0.0410. The haplotype block 2 defines the last six exons of the P2RX7 gene, hence supporting the prior single marker analysis. More...	Negative
rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912 - rs3751144 - rs3751143 - rs1653625	T-G-A-C-A-C-A-A	P2RX7	chi-square P-value = 0.095, LRS (global P-value)=0.041	We identified global significant P-values for blocks 2 with ...... We identified global significant P-values for blocks 2 with P-value = 0.0410. The haplotype block 2 defines the last six exons of the P2RX7 gene, hence supporting the prior single marker analysis. More...	Negative
rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912 - rs3751144 - rs3751143 - rs1653625	C-A-G-C-A-C-A-C	P2RX7	chi-square P-value = 0.159, LRS (global P-value)=0.041	We identified global significant P-values for blocks 2 with ...... We identified global significant P-values for blocks 2 with P-value = 0.0410. The haplotype block 2 defines the last six exons of the P2RX7 gene, hence supporting the prior single marker analysis. More...	Negative
rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912 - rs3751144 - rs3751143 - rs1653625	C-G-G-C-A-C-C-C	P2RX7	chi-square P-value = 0.979, LRS (global P-value)=0.041	We identified global significant P-values for blocks 2 with ...... We identified global significant P-values for blocks 2 with P-value = 0.0410. The haplotype block 2 defines the last six exons of the P2RX7 gene, hence supporting the prior single marker analysis. More...	Negative
rs208293 - rs208294 - rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912	T-C-T-G-A-C-A	P2RX7	chi-square P-value = 0.06, LRS (global P-value)=0.0178 with a sliding window strategy	The 7-SNP positively associated haplotype window bordered by...... The 7-SNP positively associated haplotype window bordered by P2RX7-I04B and P2RX7-E13A overlaps blocks 1 and 2 and is characterized by a haplotype strictly observed in the case group (P-value = 0.0006) bearing the mutated allele for the non-synonymous SNP P2RX7-E08A. More...	Negative
rs208293 - rs208294 - rs504677 - rs7958311 - rs1718119 - rs6489795 - rs2230912	T-C-T-G-A-C-G	P2RX7	chi-square P-value = 0.048, LRS (global P-value)=0.0178 with a sliding window strategy	The 7-SNP positively associated haplotype window bordered by...... The 7-SNP positively associated haplotype window bordered by P2RX7-I04B and P2RX7-E13A overlaps blocks 1 and 2 and is characterized by a haplotype strictly observed in the case group (P-value = 0.0006) bearing the mutated allele for the non-synonymous SNP P2RX7-E08A. More...	Positive
rs1653625 - rs4980999 - rs3817190 - rs28360477	C-C-T-C	P2RX4 CAMKK2	chi-square P-value = 0.012, LRS (global P-value)=0.039	We identified global significant P-values for blocks 4 with ...... We identified global significant P-values for blocks 4 with P-value = 0.0390. The haplotype block 4 encloses the associated SNP P2RX4-UTR3A, hence supporting the prior single marker analysis. More...	Positive
rs1653625 - rs4980999 - rs3817190 - rs28360477	G-C-T-C	P2RX4 CAMKK2	chi-square P-value = 0.065, LRS (global P-value)=0.039	We identified global significant P-values for blocks 4 with ...... We identified global significant P-values for blocks 4 with P-value = 0.0390. The haplotype block 4 encloses the associated SNP P2RX4-UTR3A, hence supporting the prior single marker analysis. More...	Negative
rs1653625 - rs4980999 - rs3817190 - rs28360477	C-C-A-C	P2RX4 CAMKK2	chi-square P-value = 0.314, LRS (global P-value)=0.039	We identified global significant P-values for blocks 4 with ...... We identified global significant P-values for blocks 4 with P-value = 0.0390. The haplotype block 4 encloses the associated SNP P2RX4-UTR3A, hence supporting the prior single marker analysis. More...	Negative
rs1653625 - rs4980999 - rs3817190 - rs28360477	G-C-A-T	P2RX4 CAMKK2	chi-square P-value = 0.235, LRS (global P-value)=0.039	We identified global significant P-values for blocks 4 with ...... We identified global significant P-values for blocks 4 with P-value = 0.0390. The haplotype block 4 encloses the associated SNP P2RX4-UTR3A, hence supporting the prior single marker analysis. More...	Negative
rs1653625 - rs4980999 - rs3817190 - rs28360477	C-T-T-C	P2RX4 CAMKK2	chi-square P-value = 0.179, LRS (global P-value)=0.039	We identified global significant P-values for blocks 4 with ...... We identified global significant P-values for blocks 4 with P-value = 0.0390. The haplotype block 4 encloses the associated SNP P2RX4-UTR3A, hence supporting the prior single marker analysis. More...	Negative

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

Gene	Statistical Values/Author Comments	Result Category
CAMKK2	Allelic, genotypic or family-based association studies suggest the presence of two susceptibility lo...... Allelic, genotypic or family-based association studies suggest the presence of two susceptibility loci, the P2RX7 and CaMKK2genes. More...	Positive
P2RX7	Allelic, genotypic or family-based association studies suggest the presence of two susceptibility lo...... Allelic, genotypic or family-based association studies suggest the presence of two susceptibility loci, the P2RX7 and CaMKK2genes. More...	Positive

Gene-gene interactions reported by this study for BD (count: 2)

Gene Group	Markers	Statistical Values	Author Comments	Result Category
P2RX7 CAMKK2	rs1653625 - rs28360463 - rs1653622 - rs11065500 - rs11065501 - rs4980999 - rs3817190	Haplotype cross these two genes were tested. For haplotype "A-A-G-G-C-T-T", chi-square P-value = 0.362, LRS (global P-value) = 0.0249 with a sliding window strategy; For haplotype "A-C-A-A-C-C-A", chi-square P-value = 0.685, LRS (global P-value) = 0.0249 with a sliding window strategy; For haplotype "A-C-A-A-C-C-T", chi-square P-value = 0.487, LRS (global P-value) = 0.0249 with a sliding window strategy; For haplotype "A-C-A-A-C-T-T", chi-square P-value = 0.544, LRS (global P-value) = 0.0249 with a sliding window strategy; For haplotype "A-C-A-A-G-C-A", chi-square P-value = 0.106, LRS (global P-value) = 0.0249 with a sliding window strategy; For haplotype "A-C-A-A-G-C-T", chi-square P-value = 0.073, LRS (global P-value) = 0.0249 with a sliding window strategy; For haplotype "A-C-G-A-C-C-A", chi-square P-value = 0.163, LRS (global P-value) = 0.0249 with a sliding window strategy; For markers "A-C-G-A-C-C-T", chi-square P-value = 0.327, LRS (global P-value) = 0.0249 with a sliding window strategy; For haplotype "C-C-A-A-C-C-T", chi-square P-value = 0.012, LRS (global P-value) = 0.0249 with a sliding window strategy.	The other 7-SNP positively associated window bordered by mar...... The other 7-SNP positively associated window bordered by markers P2RX7-UTR3A and CAMKK2-E01B comprises blocks 3 and 4 and the associated marker P2RX4-UTR3A. More...	Positive
P2RX4 CAMKK2	rs1653625 - rs4980999 - rs3817190 - rs28360477	Haplotype cross these two genes were tested. For haplotype "C-C-T-C", chi-square P-value = 0.012, LRS (global P-value) = 0.039; For haplotype "C-C-A-C", chi-square P-value = 0.314, LRS (global P-value) = 0.039; For haplotype "G-C-T-C", chi-square P-value = 0.065, LRS (global P-value) = 0.039; For haplotype "C-T-T-C", chi-square P-value = 0.179, LRS (global P-value) = 0.039; For haplotype "G-C-A-T", chi-square P-value = 0.235, LRS (global P-value) = 0.039; For haplotype "G-C-A-C", chi-square P-value = 0.411, LRS (global P-value) = 0.039.	We identified global significant P-values for blocks 4 with ...... We identified global significant P-values for blocks 4 with P-value = 0.0390. The haplotype block 4 encloses the associated SNP P2RX4-UTR3A, hence supporting the prior single marker analysis. More...	Positive