title: Effect of childhood general traumas on suicide attempt depends on TPH2 and ADARB1 variants in psychiatric patients.
abstract: Suicidal behavior has been associated with a deficient serotonin neurotransmission which is likely a consequence of individual genetic architecture, exposure to environmental factors and interactions of those factors. We examined whether the interaction of child abuse, TPH2 (tryptophan hydroxylase 2) variant rs4290270, affecting alternative splicing and editing of TPH2 pre-mRNAs, and ADARB1 (adenosine deaminase acting on RNA B1) variants rs4819035 and rs9983925 may influence the risk for suicide attempt in psychiatric patients. TPH2 rs4290270 was genotyped in 165 suicide attempters and 188 suicide non-attempters diagnosed with major depressive disorder, bipolar disorder and schizophrenia. Genotyping data for ADARB1 variants were taken over from our previous study. Child abuse before the age of 18 years was assessed using the Early Trauma Inventory-Self Report. Generalized linear models and backward selection were applied to identify the main and interacting effects of environmental and genetic factors, including psychiatric diagnoses, patients' gender and age as covariates. Childhood general traumas were independently associated with suicide attempt. Two-way interaction between TPH2 rs4290270 and general traumas revealed that TT homozygotes with a history of general traumas had an increased risk for suicide attempt. Three-way interaction of general traumas, TPH2 rs4290270 and ADARB1 rs4819035 indicated that the highest predisposition to suicide attempt was observed in individuals who experienced general traumas and were TT homozygote for rs4290270 and TT homozygote for rs4819035. Our findings suggest that the risk for suicide attempt in psychiatric patients exposed to an adverse childhood environment may depend on TPH2 and ADARB1 variants.
authors.affiliation: Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Studentski trg 16, PO box 43, Belgrade, 11000, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Karanović
authors.affiliation: Clinic for Psychiatry, Clinical Centre of Serbia, Pasterova 2, Belgrade, 11000, Serbia.|Medical School, University of Belgrade, Doktora Subotića 8, Belgrade, 11000, Serbia.
authors.forename: Maja
authors.initials: M
authors.lastname: Ivković
authors.affiliation: Department of Genetic Research, Institute for Biological Research "Siniša Stanković", University of Belgrade, Bulevar despota Stefana 142, Belgrade, 11000, Serbia.
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Jovanović
authors.affiliation: Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Studentski trg 16, PO box 43, Belgrade, 11000, Serbia.
authors.forename: Saša
authors.initials: S
authors.lastname: Šviković
authors.affiliation: Clinic for Psychiatry, Clinical Centre of Serbia, Pasterova 2, Belgrade, 11000, Serbia.
authors.forename: Maja
authors.initials: M
authors.lastname: Pantović-Stefanović
authors.affiliation: Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Studentski trg 16, PO box 43, Belgrade, 11000, Serbia.
authors.forename: Miloš
authors.initials: M
authors.lastname: Brkušanin
authors.affiliation: Clinic for Psychiatry, Clinical Centre of Serbia, Pasterova 2, Belgrade, 11000, Serbia.|Medical School, University of Belgrade, Doktora Subotića 8, Belgrade, 11000, Serbia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Damjanović
authors.affiliation: Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Studentski trg 16, PO box 43, Belgrade, 11000, Serbia.
authors.forename: Goran
authors.initials: G
authors.lastname: Brajušković
authors.affiliation: Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Studentski trg 16, PO box 43, Belgrade, 11000, Serbia. duska@bio.bg.ac.rs.
authors.forename: Dušanka
authors.initials: D
authors.lastname: Savić-Pavićević
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D054523:Adult Survivors of Child Abuse; D005260:Female; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D060005:Genotyping Techniques; D006801:Humans; D016014:Linear Models; D008297:Male; D001523:Mental Disorders / Q000235:genetics* / Q000523:psychology*; D020033:Protein Isoforms; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D012565:Schizophrenic Psychology; D013406:Suicide, Attempted; D014365:Tryptophan Hydroxylase / Q000235:genetics* / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D016601:RNA-Binding Proteins; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase
keywords: Child abuse; Gene–environment interaction; RNA editing; Suicide attempted; Tryptophan hydroxylase; rs4290270