DRD4 and susceptibility to peer influence on alcohol use from adolescence to adulthood
Introduction
Both social environment and genetic factors have long been implicated in alcohol use (Kendler et al., 2008, Zucker, 2006). Recent studies also point to the presence of gene by environment (G × E) interactions, such as specific genetic polymorphisms being associated with increased susceptibility to environmental influences (Belsky and Pluess, 2009). One genetic polymorphism of interest in the alcoholism literature is the number of variable number tandem repeats (VNTR) in the third exon of the DRD4 dopamine receptor gene. The presence of a long DRD4 allele (involving 7+ repeats) decreases dopamine reception efficiency (Asghari et al., 1995) and has been linked with increased craving in response to alcohol cues (McGeary, 2009; Ray et al., 2010), greater alcohol use (Vaughn et al., 2009), and personality correlates of alcohol use such as thrill seeking (Dmitrieva et al., 2011), as well as other types of problem and addictive behaviors such as delinquency (Boutwell and Beaver, 2008) and smoking (Hutchison et al., 2002). This study examines the interaction of DRD4 polymorphism with a key environmental factor in alcohol use – peer drinking (Windle, 2000), across several developmental periods from adolescence through young adulthood.
A sizeable literature also indicates that the DRD4 polymorphism interacts with environmental influences. For instance, young children with the long DRD4 allele are more sensitive to both positive and negative aspects of parental and non-parental care (Bakermans-Kranenburg and van IJzendoorn, 2011, Belsky and Pluess, 2013). These effects extend to prenatal exposure to maternal stress (Zohsel et al., 2014) and persist developmentally into adolescence (Nikitopoulos et al., 2014). These interactions have also been found in adulthood, with male carriers of the long DRD4 allele being more sensitive to the positive effects of long-term romantic relationships on desisting from delinquency (Beaver et al., 2008).
Since substance use does not emerge developmentally before adolescence, the role of DRD4 in substance use and addiction can be studied only in adolescents and adults. In studies examining alcohol use, peer influences on heavy drinking were stronger among young adults (age 18–28) with the long DRD4 allele (Larsen et al., 2010). Similarly, emerging adults involved in college or Greek organizations who had the long DRD4 allele reported more alcohol dependence symptoms (Park et al., 2011). However, another study with adolescents (ages 13–18) failed to find increased susceptibility to peer influences on alcohol use among those with high risk DRD4 polymorphism (van der Zwaluw et al., 2012), and parenting influences on regular alcohol (or cannabis) use did not vary across DRD4 genotypes in another adolescent study (Creemers et al., 2011). Similarly conflicting results have been reported for smoking outcomes. For instance, adults with the long DRD4 allele smoked more in response to smoking cues and negative affect induction (Hutchison et al., 2002, Perkins et al., 2008), but the effects of smoking-related parenting behaviors on adolescent smoking outcomes did not vary across DRD4 genotypes (Hiemstra et al., 2013).
Applying a developmental perspective to these mixed findings, a relatively consistent picture emerges. Significant interactions between DRD4 and environmental influences are more often found in early childhood and in adulthood, but less so in adolescence. One study with adolescents even found the opposite pattern of interactions, with carriers of the long DRD4 allele being less sensitive to the effects of peer victimization and social well-being on delinquency (Kretschmer et al., 2013). For alcohol use specifically, behavior genetic studies show a clear developmental pattern of primarily environmental influences on alcohol use in adolescence, followed by an increasing role of genetic factors in adulthood (Dick et al., 2006, Kendler et al., 2008). These results suggest that G × E interactions, including those involving DRD4, may not emerge in adolescence when genetic influences on alcohol use are minimal. Together, studies on DRD4 by environment interactions across developmental periods and behavior genetic studies of alcohol use suggest that interactions between DRD4 and peer drinking may manifest developmentally later in adulthood, but not in adolescence.
The present study examines developmental differences in the interactive effects of DRD4 polymorphism and friends’ drinking on alcohol use across four developmental phases: late adolescence (ages 16–18), emerging adulthood (ages 20–25), early young adulthood (ages 26–30), and later young adulthood (ages 30–35). Because the relationship between peer and own alcohol use is dynamic and involves both selection of friends with similar drinking habits and peer influence (Burk et al., 2012), we model both types of mechanisms (peer selection and socialization) across the developmental periods examined. We also include two related, yet distinct alcohol use outcomes – levels of alcohol use (standard quantity–frequency index) and heavy episodic (or binge) drinking. By examining two alcohol phenotypes across four developmental periods, we are able to determine the developmental and phenotype-related specificity of the DRD4 by peer drinking interactions.
Section snippets
Study design and participants
The sample includes 340 participants (59% female; 98% White, 0.9% Black, 0.6% Hispanic, 0.3% Native American and 0.3% Other) who were assessed four times between mean ages 17 and 33. These participants are a subsample from the Lives Across Time: A Longitudinal Study of Adolescent and Adult Development (LAT; Windle and Wiesner, 2004). The larger study recruited 1210 high school students (participation rate 76%) from suburban public schools in western New York. The youth were assessed 3–4 times
Results
The allele and genotype frequencies for DRD4 are provided in Table 1. The distributions of the allele and genotype frequencies, and the short-long genotype classification are consistent with prior research with Caucasian and European samples (Hutchison et al., 2003, van der Zwaluw et al., 2012) as well as with European samples reported in the Allele Frequency Database (Rajeevan et al., 2012). We did not collect data on ancestry informative markers and relied on self-reports of ethnicity.
Discussion
This study used a prospective design to examine G × E interaction between friends’ alcohol use and DRD4 genotype in predicting alcohol use and heavy drinking from adolescence to later young adulthood. The analyses modeled the reciprocal processes of peer selection and socialization over time, as well as continuity in own and friends’ alcohol use and any differences in these relationships by DRD4 polymorphism. The results revealed the presence of an interaction between DRD4 and friends’ alcohol
Role of funding source
Funding for this study was provided by NIAAA Grant AA07861. NIAAA had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication.
Contributors
Sylvie Mrug reviewed the literature, conceptualized the study, conducted statistical analyses and drafted and revised the manuscript. Michael Windle directed that LAT study and contributed to the conceptualization, drafting and revisions of the manuscript.
Conflict of interest
No conflict declared.
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2016, Child and Adolescent Psychiatric Clinics of North AmericaCitation Excerpt :Research on genetic polymorphisms of several genes are underway, including but not limited to dopamine receptor gene (DRD4), serotonin transporter gene (5-HTTPLR), Mu-opioid receptor gene (OPRM1), aldehyde dehydrogenase (ALDH 2), and gamma amino butyric acid receptor (GABRA2), which show strong linkage with alcohol use among adolescents.37 Interestingly, these candidate genes are also linked to impulsivity and anxiety, which also place the youth with these traits more vulnerable to problematic use.38,39 Understanding these genetic influences that influence drinking behaviors is an evolving field40 that may have implications for developing interventions specific to genotypes.