title: P2RX7: A bipolar and unipolar disorder candidate susceptibility gene?
abstract: The chromosomal region 12q24 has been previously implicated by linkage studies of both bipolar disorder and unipolar mood disorder and we have reported two pedigrees segregating both bipolar disorder and Darier's disease that show linkage across this region. The gene P2RX7 is located in this chromosomal region and has been recently reported as a susceptibility gene for bipolar disorder and unipolar depression. The non-synonymous SNP rs2230912 (resulting in amino-acid polymorphism Q460R) showed the strongest association and has been postulated to be pathogenically relevant. We have investigated this gene in a large UK case-control sample (bipolar I disorder N = 687, unipolar recurrent major depression N = 1,036, controls N = 1,204). Neither rs2230912 nor any of 8 other SNPs genotyped across P2RX7 was found to be associated with mood disorder in general, nor specifically with bipolar or unipolar disorder. Further, sequencing of our two chromosome 12-linked bipolar-Darier families showed no evidence of rare variants at P2RX7 that could explain the linkage. Our data do not provide support for rs2230912 or the other polymorphisms studied within the P2RX7 locus, being involved in susceptibility to mood disorders.
authors.affiliation: Department of Psychological Medicine, Wales College of Medicine, Cardiff University, Heath Park, UK. greenek@cf.ac.uk
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Green
authors.forename: Detelina
authors.initials: D
authors.lastname: Grozeva
authors.forename: Rachel
authors.initials: R
authors.lastname: Raybould
authors.forename: Gareth
authors.initials: G
authors.lastname: Elvidge
authors.forename: Stuart
authors.initials: S
authors.lastname: Macgregor
authors.forename: Ian
authors.initials: I
authors.lastname: Craig
authors.forename: Anne
authors.initials: A
authors.lastname: Farmer
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.forename: Liz
authors.initials: L
authors.lastname: Forty
authors.forename: Lisa
authors.initials: L
authors.lastname: Jones
authors.forename: Ian
authors.initials: I
authors.lastname: Jones
authors.forename: Mick C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Mike J
authors.initials: MJ
authors.lastname: Owen
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
mesh_terms: D019943:Amino Acid Substitution; D001714:Bipolar Disorder / Q000235:genetics; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12; D003866:Depressive Disorder / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058486:Receptors, Purinergic P2X7; D006113:United Kingdom
chemical_list: C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7