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	McQuillin, A.,2009 PMID: 18268501
Citation	McQuillin, A., N. J. Bass, et al. (2009). Case-control studies show that a non-conservative amino-acid change from a glutamine to arginine in the P2RX7 purinergic receptor protein is associated with both bipolar- and unipolar-affective disorders. Mol Psychiatry 14(6): 614-620.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	613 bipolar individuals with 560 psychiatrically screened normal controls.
SNP/Region/Marker Size	7 SNPs and 2 variants
Predominant Ethnicity	Caucasian
Population	British and Irish

Detail Info

Sample Diagnosis	RDC
Sample Status	The UK/UCL sample consisted of 613 bipolar individuals with 560 psychiatrically screened normal controls. To address the issue of population stratification,participation was restricted to individuals of UK and Irish background. Individuals with not more than one grandparent of other Western European ancestry were also included. UK National Health Service Multicentre Research Ethics Committee approval was obtained and all subjects signed a consent form after reading an information sheet. All subjects were interviewed using the lifetime version of the Schizophrenia and Affective Disorders Schedule and assigned a research diagnostic criteria (RDC) diagnosis.Altogether 97% of the bipolar sample consisted of bipolar 1 cases and 3% were bipolar 2 subtype.Therefore 97% of our sample had psychotic features with manic syndrome and were diagnosed as bipolar 1 according to RDC and diagnostic and statistical manual III revised (DSMIIIR) criteria.
Technique	genotyping
Statistical Method	SNP and microsatellite data were tested for allelic association using X² and empirical CLUMP32 methods of analysis.GENECOUNTING was used for tests of marker to marker linkage disequilibrium (LD) and tests of haplotypic association with permutation.Analysis of haplotype block structure and individual haplotype association tests were performed using HAPLOVIEW.
Result Summary	We have confirmed the allelic associations between bipolar disorder and the markers rs2230912(P2RX7-E13A, G allele, P = 0.043) and NBG6 (P = 0.010) in a London-based sample of 604 bipolar cases and 560 controls. When we combined these data with the published case-control studies of P2RX7 and mood disorder (3586 individuals) the association between rs2230912 (Gln460Arg) and affective disorders became more robust (P = 0.002). The increase in Gln460Arg was confined to heterozygotes rather than homozygotes suggesting a dominant effect (odds ratio 1.302, CI = 1.129-1.503). Although further research is needed to prove that the Gln460Arg change has an aetiological role, it is so far the most convincing mutation to have been found with a role for increasing susceptibility to bipolar and genetically related unipolar disorders.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs504677	P2RX7			Allelic Association: X²=0.288, P-value = 0.591	No significant association was observed No significant association was observed	Negative
rs2230912	P2RX7			Allelic Association: X²=4.093, P-value = 0.043	Significant association was observed Significant association was observed	Positive
rs3817190	CAMKK2			Allelic Association: X²=0.018, P-value = 0.893	No significant association was observed No significant association was observed	Negative
rs208293	P2RX7			Allelic Association: X²=3.346, P-value = 0.067	No significant association was observed No significant association was observed	Negative
rs208294	P2RX7			Allelic Association: X²=0.29, P-value = 0.59	No significant association was observed No significant association was observed	Negative
rs11065501	CAMKK2 P2RX4			Allelic Association: X²=0.213, P-value = 0.644	No significant association was observed No significant association was observed	Negative
rs1718119	P2RX7			Allelic Association: X²=0.336, P-value = 0.562	No significant association was observed No significant association was observed	Negative

Haplotypes reported by this study for BD (count: 6)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs1718119 - rs2230912		P2RX7	Haplotypic association:Global LRT=9.52, df=3, Global empirical P-value = 0.019	Significant association with BPD was found. Significant association with BPD was found.	Positive
rs208293 - rs1718119 - rs2230912 - rs11065501		P2RX7	Haplotypic association:Global LRT=29.02, df=13, Global empirical P-value = 0.0037	Significant association with BPD was found. Significant association with BPD was found.	Positive
rs208294 - rs504677 - rs2230912		P2RX7	Haplotypic association:Global LRT=14.96, df=7, Global empirical P-value = 0.029	Significant association with BPD was found. Significant association with BPD was found.	Positive
rs504677 - rs2230912		P2RX7	Haplotypic association:Global LRT=11.88, df=3, Global empirical P-value = 0.0079	Significant association with BPD was found. Significant association with BPD was found.	Positive
rs208293 - rs504677 - rs1718119 - rs2230912 - rs11065501		P2RX7	Haplotypic association:Global LRT=42.66, df=22, Global empirical P-value = 0.0041	Significant association with BPD was found. Significant association with BPD was found.	Positive
rs208293 - rs504677 - rs2230912 - rs11065501		P2RX7	Haplotypic association:Global LRT=28.04, df=15, Global empirical P-value = 0.011	Significant association with BPD was found. Significant association with BPD was found.	Positive

Other variants reported by this study for BD (count: 2)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
P2RX7 P2RX73	P2RX7	duplication	tetra-nucleotide repeat		Allelic Association:P-value = 0.190	No significant associations were found. No significant associations were found.	Negative
P2RX7 NBG6	P2RX7	microsatellite	multi-allelic microsatellite		Allelic Association:P-value = 0.010	Significant associations were found in BP. Significant associations were found in BP.	Positive

Genes reported by this study for BD (count: 3)

Gene	Statistical Values/Author Comments	Result Category
P2RX7	We set out to replicate the association findings with P2RX7 in our UK bipolar disorder case-control ...... We set out to replicate the association findings with P2RX7 in our UK bipolar disorder case-control sample and to carry out a combined analysis of previous studies.Our results largely confirm the previous findings and strengthen the evidence for a role for P2RX7 in susceptibility to mood disorders. More...	Positive
CAMKK2	No significant association was observed with BP. No significant association was observed with BP.	Negative
P2RX4	No significant association was observed with BP. No significant association was observed with BP.	Negative