title: P2RX7 gene is associated consistently with mood disorders and predicts clinical outcome in three clinical cohorts.
abstract: We investigated the effect of nine candidate genes on risk for mood disorders, hypothesizing that predisposing gene variants not only elevate the risk for mood disorders but also result in clinically significant differences in the clinical course of mood disorders. We genotyped 178 DSM-IV bipolar I and II and 272 major depressive disorder patients from three independent clinical cohorts carefully diagnosed with semistructured interviews and prospectively followed up with life charts for a median of 60 (range 6-83) months. Healthy control subjects (n = 1322) were obtained from the population-based national Health 2000 Study. We analyzed 62 genotyped variants within the selected genes (BDNF, NTRK2, SLC6A4, TPH2, P2RX7, DAOA, COMT, DISC1, and MAOA) against the presence of mood disorder, and in post-hoc analyses, specifically against bipolar disorder or major depressive disorder. Estimates for time ill were based on life charts. The P2RX7 gene variants rs208294 and rs2230912 significantly elevated the risk for a familial mood disorder (OR = 1.35, P = 0.0013, permuted P = 0.06, and OR = 1.44, P = 0.0031, permuted P = 0.17, respectively). The results were consistent in all three cohorts. The same risk alleles predicted more time ill in all cohorts (OR 1.3, 95% CI 1.1-1.6, P = 0.0069 and OR 1.7, 95% CI 1.3-2.3, P = 0.0002 with rs208294 and rs2230912, respectively), so that homozygous carriers spent 12 and 24% more time ill. P2RX7 and its risk alleles predisposed to mood disorders consistently in three independent clinical cohorts. The same risk alleles resulted in clinically significant differences in outcome of patients with major depressive and bipolar disorder.
authors: Public Health Genomics Unit, Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland.
authors: Pia
authors: P
authors: Soronen
authors: Outi
authors: O
authors: Mantere
authors: Tarja
authors: T
authors: Melartin
authors: Kirsi
authors: K
authors: Suominen
authors: Maria
authors: M
authors: Vuorilehto
authors: Heikki
authors: H
authors: Rytsälä
authors: Petri
authors: P
authors: Arvilommi
authors: Irina
authors: I
authors: Holma
authors: Mikael
authors: M
authors: Holma
authors: Pekka
authors: P
authors: Jylhä
authors: Hanna M
authors: HM
authors: Valtonen
authors: Jari
authors: J
authors: Haukka
authors: Erkki
authors: E
authors: Isometsä
authors: Tiina
authors: T
authors: Paunio
mesh_terms: D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019964:Mood Disorders / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D058486:Receptors, Purinergic P2X7 / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7