Initial Evidence of an Association Between OPRM1 and Adolescent Alcohol Misuse

Abstract

Background Considerable research efforts have attempted to identify genes associated with alcoholism among adults, yet few studies have examined adolescents. Identifying genes associated with alcohol misuse in youth is important given that the relative contribution of genetic and environmental influences on alcoholism varies across development. The purpose of this study was to examine the association between a polymorphism of the μ-opioid receptor gene (OPRM1) and alcohol misuse in a sample of youth and to test whether heightened sensitivity to the reinforcing effects of alcohol mediated this relationship. Methods Adolescents (n = 187; mean age = 15.4 years; 47.6% female) were genotyped for A118G (rs1799971), a single-nucleotide polymorphism (SNP) of the OPRM1 gene, and assessed for alcohol use disorder (AUD) diagnoses and other psychopathology. Alcohol misuse was also measured continuously to maximize detection of drinking problems in youth. Drinking motives were used to capture the extent to which youth consumed alcohol to enhance positive affect. Results AUD groups differed significantly in terms of allelic distributions of the A118G SNP, such that 51.9% of youth with an AUD carried at least one copy of the G allele compared to 16.3% of non-AUD controls. Those who carried the G allele endorsed drinking to enhance positive affect more strongly than those who were homozygous for the A allele and drinking to enhance positive affect mediated the association between OPRM1 and alcohol-related problems. Conclusions These data build on findings from adult studies and provide the first evidence that a polymorphism of the OPRM1 receptor gene is associated with the development of early-onset alcohol-related problems during adolescence, in part, by heightening sensitivity to the reinforcing effects of alcohol.

Genetic influences on adolescent behavior

“…For instance, DRD4 , a dopamine receptor gene, has been linked to both heavy (Laucht et al, 2007) and binge (Vaughn et al, 2009) adolescent drinking as well as conduct disorder (Mota et al, 2013). A mu-opioid receptor gene, OPRM1 , has been implicated in both alcohol misuse (Miranda et al, 2010) and “antisocial drug dependence” (Corley et al, 2008). The nicotonic receptor family has also been implicated in antisocial behavior and drug use ( CHRNA2, Corley et al, 2008) and adolescent binge drinking ( CHRNA4 , Coon et al, 2014).…”

Pharmacogenetics of OPRM1

“…Adolescents with the A/G or G/G genotypes at A118G are three times more likely to have an alcohol use disorder than those with the A/A genotype [83, 84]. Two studies have also found an association between A118G genotype and alcohol dependence in adult Caucasians; however, one found the G allele to be protective while the other found carriers of the G allele to be at increased risk [85, 86].…”

The Role of the Asn40Asp Polymorphism of the Mu Opioid Receptor Gene (OPRM1) on Alcoholism Etiology and Treatment: A Critical Review

“…While the vast majority of the studies have focused on adult samples, a recent study examining AUD in a sample of adolescents reported a significantly higher frequency of the Asp40 allele among youth with AUD (51.9%), as compared to non-AUD controls (16.3%) (Miranda et al, 2010). Asp40 carriers in this sample were more likely to endorse drinking motives related to the enhancement of positive affect, which in turn mediated the association between OPRM1 genotype and AUD status (Miranda et al, 2010).…”