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Exploring epistasis in candidate genes for antisocial personality disorder

Arias, JMC; Acosta, CAP; Valencia, JG; Montoya, GJ; Viana, JCA; Nieto, OC; Florez, AF; ... Ruiz-Linares, A; + view all (2011) Exploring epistasis in candidate genes for antisocial personality disorder. PSYCHIAT GENET , 21 (3) 115 - 124. 10.1097/YPG.0b013e3283437175.

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Abstract

Objective To identify and characterize high-order gene-to-gene interactions in antisocial personality disorder (ASPD).Methods Participants for case-control study were selected from the inmate male population in Bellavista prison from Medellin. The study included 310 individuals with ASPD and 200 with no ASPD. Diagnoses were made according to a best-estimate procedure based on a semistructured interview (diagnostic interview for genetic studies 3.0). We genotyped some single-nucleotide polymorphisms in candidate genes with main serotonin pathway effects. The gene-gene interaction was examined using the multifactor dimensionality reduction method version 2.0.alpha. We assessed model sizes of 2 and 3 loci and counted the number of replicates that contained the causal loci in the final best model that was identified using 10-fold cross validation.Results We find epistatic interaction with catechol-O-methyl transferase (COMT), tryptophan hydroxylase, and 5-HTR2A (serotonin receptor) with ASPD. This data supports an important role of polymorphism in serotonin receptors and low enzyme activity of COMT for susceptibility to ASPD.Conclusion This study suggests that gene interactions between genetic variants in COMT, 5-HTR2A and tryptophan hydroxylase gene would be associated with ASPD and influence the dopamine rewards pathways and modulate serotonin levels in ASPD. Psychiatr Genet 21: 115-124 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Type: Article
Title: Exploring epistasis in candidate genes for antisocial personality disorder
DOI: 10.1097/YPG.0b013e3283437175
Keywords: antisocial personality disorder, candidate genes, epistasis, genetic association, multifactor dimensionality reduction, DEFICIT-HYPERACTIVITY DISORDER, TRYPTOPHAN-HYDROXYLASE GENE, O-METHYLTRANSFERASE GENE, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, Y-CHROMOSOME DIVERSITY, 5-HT2A RECEPTOR GENE, PROMOTER REGION, FUNCTIONAL POLYMORPHISM, A218C POLYMORPHISM, T102C POLYMORPHISM
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1310577
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