Evidence map›Paper›PMID 18268501›Full record

ArticleMolecular psychiatry2009

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.

A McQuillin, N J Bass, K Choudhury, V Puri, M Kosmin, J Lawrence, D Curtis, H M D Gurling

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Molecular psychiatry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 2 pooled it
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 116 citations in OpenAlex.

  1. Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics.Progress in neuro-psychopharmacology & biological psychiatry · 2015
    Pooled it
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  18. The P2X7 Receptor: Central Hub of Brain Diseases.Frontiers in molecular neuroscience · 2020
    Review
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  20. P2X7 Interactions and Signaling - Making Head or Tail of It.Frontiers in molecular neuroscience · 2019
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

A McQuillinMolecular Psychiatry Laboratory, Department of Mental Health Sciences, Windeyer Institute of Medical Sciences, Royal Free and University College Medical School, University College London, London, UK.
N J Bass
K Choudhury
V Puri
M Kosmin
J Lawrence
D Curtis
H M D Gurling
The Royal Free Hospital · GBUniversity College London · GBQueen Mary University of London · GB

Funding

Medical Research Council G0500791Medical Research Council G1000708Medical Research Council G9623693N
6 · The paper itself

Abstract

Three linkage studies of bipolar disorder have implicated chromosome 12q24.3 with lod scores of over 3.0 and several other linkage studies have found lods between 2 and 3. Fine mapping within the original chromosomal linkage regions has identified several loci that show association with bipolar disorder. One of these is the P2RX7 gene encoding a central nervous system-expressed purinergic receptor. A non-synonymous single nucleotide polymorphism, rs2230912 (P2RX7-E13A, G allele) and a microsatellite marker NBG6 were both previously found to be associated with bipolar disorder (P=0.00071 and 0.008, respectively). rs2230912 has also been found to show association with unipolar depression. The effect of the polymorphism is non-conservative and results in a glutamine to arginine change (Gln460Arg), which is likely to affect P2RX7 dimerization and protein-protein interactions. 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.

Indexed as

Linkage DisequilibriumAmino Acid SubstitutionArginineBipolar DisorderCase-Control StudiesChromosomes, Human, Pair 12Depressive DisorderGene FrequencyGenes, DominantGenetic Predisposition to DiseaseGlutamineHaplotypesHeterozygoteHomozygoteHumansMicrosatellite RepeatsArginineGlutamineP2RX7 protein, humanReceptors, Purinergic P2Receptors, Purinergic P2X7

Identifiers

PMID18268501
OpenAlexW2044259424

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.