ORIGINAL ARTICLESExploring epistasis in candidate genes for antisocial personality disorderCuartas Arias, Jorge Mauricioa,b; Palacio Acosta, Carlos A.a; Valencia, Jenny Garciaa; Montoya, Gabriel J.a; Arango Viana, Juan C.a; Nieto, Omer Campob; Flórez, Andrés F.c; Camarena Medellin, Beatriz E.d; Montoya, Winston Rojasb; Lopez Jaramillo, Carlos A.a; Achury, Javier Gutierrezb; Fuentes, Carlos Cruzd; Berrio, Gabriel Bedoyab; Ruiz-Linares, Andresb,eAuthor Information aDepartment of Psychiatry, Faculty of Medicine bMolecular Genetics Group (GENMOL), Biology Institute cProgram for the Study and Control of Tropical Diseases (PECET), Universidad de Antioquia, Medellin, Colombia dNational Institute of Psychiatry, Ramón de la Fuente Muñiz, D.F. Mexico eDepartment of Genetics, Evolution and Environment, University College, London, UK Correspondence to Jorge Mauricio Cuartas Arias, MSc, PhD, Molecular Genetics Group (GENMOL) Biology Institute, University of Antioquia, Calle 62 # 52-59, Research Center (SIU), University of Antioquia, Medellin, Colombia Tel: +57 42196467; fax: +57 42196469; e-mail: firstname.lastname@example.org Received January 22, 2010 Accepted November 11, 2010 Psychiatric Genetics: June 2011 - Volume 21 - Issue 3 - p 115-124 doi: 10.1097/YPG.0b013e3283437175 Buy Metrics 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.α. 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. © 2011 Lippincott Williams & Wilkins, Inc.