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Exploring epistasis in candidate genes for antisocial personality disorder

Cuartas 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,e

doi: 10.1097/YPG.0b013e3283437175
Original Articles

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.

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: mauricio.cuartas@siu.udea.edu.co

Received January 22, 2010

Accepted November 11, 2010

© 2011 Lippincott Williams & Wilkins, Inc.