Exploring the association between the 2-repeat allele of the MAOA gene promoter polymorphism and psychopathic personality traits, arrests, incarceration, and lifetime antisocial behavior

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Abstract

A line of research has revealed that a polymorphism in the promoter region of the MAOA gene is related to antisocial phenotypes. Most of these studies examine the effects of low MAOA activity alleles (2-repeat and 3-repeat alleles) against the effects of high MAOA activity alleles (3.5-repeat, 4-repeat, and sometimes 5-repeat alleles), with research indicating that the low MAOA activity alleles confer an increased risk to antisocial phenotypes. The current study examined whether the 2-repeat allele, which has been shown to be functionally different from the 3-repeat allele, was associated with a range of antisocial phenotypes in a sample of males drawn from the National Longitudinal Study of Adolescent Health. Analyses revealed that African-American males who carried the 2-repeat allele were, in comparison with other African-American male genotypes, significantly more likely to be arrested and incarcerated. Additional analyses revealed that African-American male carriers of the 2-repeat allele scored significantly higher on an antisocial phenotype index and on measures assessing involvement in violent behaviors over the life course. There was not any association between the 2-repeat allele and a continuously measured psychopathic personality traits scale. The effects of the 2-repeat allele could not be examined in Caucasian males because only 0.1% carried it.

Highlights

► We examine the effect of the 2R allele of MAOA on a range of antisocial outcomes. ► The 2R was related to arrest, incarceration, and lifetime antisocial behavior. ► These associations were only observable for African-American males. ► Only 0.1% of Caucasian males carried the 2-repeat allele.

Introduction

A significant amount of behavioral genetic research has examined the genetic basis to antisocial behaviors (Moffitt, 2005). The results of these studies, best summarized by a number of meta-analyses, indicate that approximately 50% of the variance in measures of antisocial phenotypes is attributable to genetic factors (Ferguson, 2010, Mason and Frick, 1994, Miles and Carey, 1997, Rhee and Waldman, 2002). More recent research has begun to investigate genetic polymorphisms that might be partially responsible for producing variation in antisocial phenotypes (Caspi et al., 2002). Genes involved in neurotransmission have been identified as the most promising candidate genes for antisocial behaviors and traits (Ferguson & Beaver, 2009). Although studies have identified an association between polymorphisms in a number of neurotransmission genes and various antisocial behaviors, these associations are often plagued by the inability for follow-up studies to replicate the original findings. An important exception to the replication problem appears to be for a functional polymorphism in the monoamine oxidase A (MAOA) gene.

The MAOA gene has been mapped to the X chromosome at location Xp11.23–11.4 (Levy et al., 1989) and codes for the production of the MAOA enzyme that catabolizes certain neurotransmitters, such as dopamine and serotonin (Shih, Chen, & Ridd, 1999). The MAOA gene has a polymorphism in the promoter region that is the result of a 30 base pair (bp) variable number of tandem repeats (VNTR) in the regulatory region of the gene. This polymorphism has been shown to be functional as different alleles correspond to the production of MAOA enzymes with different activity levels (Sabol, Hus, & Hamer, 1998). Recognizing differences in transcriptional efficiency, researchers commonly pool the alleles into two groups: those that correspond to low MAOA activity and those that correspond to high MAOA functioning. In most studies, the 2-repeat allele and the 3-repeat allele are pooled together to form the low MAOA activity genotype and the 3.5-repeat allele, 4-repeat allele, and 5-repeat allele are pooled together to form the high MAOA activity genotype (Caspi et al., 2002).

The polymorphism in the promoter region of the MAOA gene has been the source of a considerable amount of research examining whether different alleles are associated with antisocial phenotypes. In a landmark study, Caspi et al. (2002) reported a link between low MAOA activity alleles and antisocial behaviors, but only among males who had been maltreated in childhood. The results of a meta-analysis seemed to confirm the association between MAOA and antisocial outcomes for maltreated males (Kim-Cohen et al., 2006). Although most of this research has revealed that MAOA only has significant effects when paired to a criminogenic environment, there is some evidence to indicate that the low MAOA activity alleles may have effects independent of environmental factors for some antisocial behaviors (Beaver, DeLisi, Vaughn, & Barnes, 2010).

Guo and his colleagues (2008) provided evidence that the MAOA gene is related to delinquent behavior in a sample of adolescents and young adults independent of environmental factors. Unlike the vast majority of research examining the effects of the MAOA gene, Guo et al. examined the effects of the 2-repeat allele against the effects of the 3-repeat allele and 5-repeat allele and against the effects of the 3.5-repeat allele and the 4-repeat allele. The results of their analysis indicated that carriers of the 2-repeat allele were at a statistically significant greater risk for engaging in serious and violent delinquency in adolescence and early adulthood. The effects were particularly marked for males. Guo et al. also conducted a functional analysis of the alleles and found that the 2-repeat allele, in comparison with 3-repeat and 4-repeat alleles, had the lowest level of promoter activity.

The results of the study by Guo et al. suggest that pooling together the 2-repeat and 3-repeat alleles may be incorrect and that the 2-repeat allele should be examined in isolation because of its functional significance. Besides this single study, though, research has yet to fully explore this possibility and thus whether the 2-repeat allele is truly a marker for antisocial phenotypes remains to be determined. The current study examines this possibility by testing for an association between the 2-repeat allele and psychopathic personality traits, the odds of being arrested, the odds of being incarcerated, and lifetime antisocial behavior in a sample of American males.

Section snippets

Participants

Data for this study were drawn from the National Longitudinal Study of Adolescent Health (Add Health; Harris, 2009). The Add Health is a four-wave prospective study of a nationally representative sample of American youth who were enrolled in middle or high school in 1994–1995. The first (N = 20,745) and second (N = 14,738) waves of data were collected when most of the respondents were adolescents. The third wave of data was collected in 2001–2002 when the subjects were young adults (N = 15,197). The

Findings

Since prior research has revealed that the distribution of the 2-repeat allele varies by race (e.g., Reti et al., 2011, Widom and Brzustowicz, 2006), the analysis begins by examining the allelic distributions by race. As Table 1 shows, the 2-repeat allele was carried by 0.1% of Caucasian males and by 5.2% of African-American males. To check the consistency of these estimates, all of the analyses were recalculated using self-reported race instead of interviewer-rated race. Importantly, research

Discussion

Studies examining the potential link between MAOA and antisocial phenotypes typically divide alleles into a high MAOA activity group and a low MAOA activity group, with the latter being associated with an increase in antisocial phenotypes for males who were maltreated as children (Caspi et al., 2002, Kim-Cohen et al., 2006). There is limited research indicating that there may be heterogeneity in the functionality of the low MAOA activity alleles with the 2-repeat allele being related to lower

Acknowledgements

This research uses data from Add Health, a program project designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris, and funded by a grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 17 other agencies. Special acknowledgment is due to Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Persons interested in obtaining data files from Add Health should contact Add

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