Genetic epistasis in female suicide attempters |
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Authors: | Fernández-Navarro Pablo Vaquero-Lorenzo Concepción Blasco-Fontecilla Hilario Díaz-Hernández Montserrat Gratacòs Mònica Estivill Xabier Costas Javier Carracedo Ángel Fernández-Piqueras José Saiz-Ruiz Jerónimo Baca-Garcia Enrique |
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Institution: | 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 |
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Abstract: | BackgroundComplex 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).MethodsGenomic 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.ResultsMultifactor 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.ConclusionsOur results suggest an epistatic interaction between genes of all monoamines and GABA in female suicide attempters. |
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Keywords: | BDNF brain-derived neurotrophic factor CNS central nervous system DBI diazepam binding inhibitor gene DRD5 dopamine receptor D5 gene GABRG3 GABA-A receptor subunit γ3 gene GWAS Genome-wide association study HWE Hardy–Weinberg Equilibrium IPDE-SQ International Personality Disorder Examination-Screening Questionnaire MAF Minor Allele Frequency MDR Multifactor Dimensionality Reduction MINI Mini International Neuropsychiatric Interview NIMH National Institute of Mental Health ORMDR Odds ratio based Multifactor Dimensionality Reduction PAH phenylalanine hydroxylase gene SNP Single Nucleotide Polymorphisms SB Suicidal Behavior |
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