title: Genetic epistasis in female suicide attempters.
abstract: BACKGROUND
  Complex behaviors such as suicidal behavior likely exhibit gene-gene interactions. The main aim of this study is to explore potential single nucleotide polymorphisms combinations with epistatic effect in suicidal behavior using a data mining tool (Multifactor Dimensionality Reduction).
  
  
  METHODS
  Genomic DNA from peripheral blood samples was analyzed using SNPlex Technology. Multifactor Dimensionality Reduction was used to detect epistatic interactions between single nucleotide polymorphisms from the main central nervous system (CNS) neurotransmitters (dopamine: 9; noradrenaline: 19; serotonin: 23; inhibitory neurotransmitters: 60) in 889 individuals (417 men and 472 women) aged 18 years or older (585 psychiatric controls without a history of suicide attempts, and 304 patients with a history of suicide attempts). Individual analysis of association between single nucleotide polymorphisms and suicide attempts was estimated using logistic regression models.
  
  
  RESULTS
  Multifactor Dimensionality Reduction showed significant epistatic interactions involving four single nucleotide polymorphisms in female suicide attempters with a classification test accuracy of 60.7% (59.1%-62.4%, 95% CI): rs1522296, phenylalanine hydroxylase gene (PAH); rs7655090, dopamine receptor D5 gene (DRD5); rs11888528, chromosome 2 open reading frame 76, close to diazepam binding inhibitor gene (DBI); and rs2376481, GABA-A receptor subunit γ3 gene (GABRG3). The multivariate logistic regression model confirmed the relevance of the epistatic interaction [OR(95% CI)=7.74(4.60-13.37)] in females.
  
  
  CONCLUSIONS
  Our results suggest an epistatic interaction between genes of all monoamines and GABA in female suicide attempters.
authors.affiliation: Cancer and Environmental Epidemiology Unit, National Centre for Epidemiology, Carlos III Institute of Health, Avenida Monforte de Lemos, 5, 28029 Madrid, Spain. pfernandezn@isciii.es
authors.forename: Pablo
authors.initials: P
authors.lastname: Fernández-Navarro
authors.forename: Concepción
authors.initials: C
authors.lastname: Vaquero-Lorenzo
authors.forename: Hilario
authors.initials: H
authors.lastname: Blasco-Fontecilla
authors.forename: Montserrat
authors.initials: M
authors.lastname: Díaz-Hernández
authors.forename: Mònica
authors.initials: M
authors.lastname: Gratacòs
authors.forename: Xabier
authors.initials: X
authors.lastname: Estivill
authors.forename: Javier
authors.initials: J
authors.lastname: Costas
authors.forename: Ángel
authors.initials: Á
authors.lastname: Carracedo
authors.forename: José
authors.initials: J
authors.lastname: Fernández-Piqueras
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Saiz-Ruiz
authors.forename: Enrique
authors.initials: E
authors.lastname: Baca-Garcia
mesh_terms: D000293:Adolescent; D000328:Adult; D026261:Diazepam Binding Inhibitor / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D058011:Multifactor Dimensionality Reduction; D010651:Phenylalanine Hydroxylase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D050641:Receptors, Dopamine D5 / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics; D013406:Suicide, Attempted
chemical_list: D026261:Diazepam Binding Inhibitor; C527987:GABRG3 protein, human; D011963:Receptors, GABA-A; D050641:Receptors, Dopamine D5; D010651:Phenylalanine Hydroxylase