Mechanisms in the relation between GABRA2 and adolescent externalizing problems

Abstract

Conduct problems, alcohol problems and hyperactive–inattentive symptoms co-occur at a high rate and are heritable in adolescence. The γ-aminobutyric acid A receptor, α2 gene (GABRA2) is associated with a broad spectrum of externalizing problems and disinhibitory-related traits. The current study tested whether two important forms of disinhibition in adolescence, impulsivity and sensation seeking, mediated the effects of GABRA2 on hyperactive–inattentive symptoms, conduct problems, and alcohol problems. Participants were assessed at two waves (11–17 and 12–18 years old; N = 292). Analyses used the GABRA2 SNP, rs279858, which tags the two complementary (yin–yang) GABRA2 haplotypes. Multiple informants reported on adolescents’ impulsivity and sensation seeking and adolescents self-reported their hyperactive–inattentive symptoms, conduct problems and lifetime alcohol problems. Impulsivity mediated the effect of GABRA2 on alcohol problems, hyperactive–inattentive symptoms, and conduct problems, whereas sensation seeking mediated the effect of GABRA2 on alcohol problems (AA/AG geno-types conferred risk). GABRA2 directly predicted adolescent alcohol problems, but the GG genotype conferred risk. Results suggest that there may be multiple pathways of risk from GABRA2 to adolescent externalizing problems, and suggest important avenues for future research.

Predicting substance use in emerging adulthood: A genetically informed study of developmental transactions between impulsivity and family conflict

“…A SNP is a variation in a single base pair within DNA. Genetic main effects for individual SNPs exist for impulsivity and related behaviors (Hamidovic, Dlugos, Skol, Palmer, & de Wit, 2009; McGue et al, 2013; Villafuerte, Strumba, Stoltenburg, Zucker, & Burmeister, 2013; Wang, Chassin, Geiser, & Lemery-Chalfant, 2015). More recently, studies have combined multiple SNPs into indices of genetic predisposition, known as polygenic risk scores.…”

Bibliometric Insights in Genetic Factors of Substance-Related Disorders: Intellectual Developments, Turning Points, and Emerging Trends

“…The literature between 2000 and 2007 showed that more attention was paid on GABRA2 and CHRNA5. The risk of GABRA2 mutations in adolescents produced externalizing problems to the development of problematic alcohol and drug use by multiple pathways (42,43). Variants in GABRA2 are associated with alcohol and nicotine dependence, representing an early risk factor to the problematic alcohol or drug use (42,(44)(45)(46).…”

A genome wide association study of fast beta EEG in families of European ancestry

“…Subsequently, associations between GABRA2, AD (Edenberg et al 2004; Lappalainen et al 2005; Covault et al , 2004; Drgon et al ., 2006; Fehr et al ., 2006; Soyka et al 2008; Enoch et al 2006, 2010; Roh et al 2011), drug dependence (Agrawal et al 2006; Enoch et al 2010; Ehlers & Gizer 2013), and externalizing behavior (Dick et al, 2013; Salvatore et al, 2015; Trucco et al, 2016; Wang et al, 2016) have been observed, indicating the potential of genetic studies of beta EEG to facilitate discovery of genes underlying disinhibitory behavior. However, the number of replicable genetic variants uncovered by this approach has been limited (Iacono et al, 2016), necessitating large scale genetic association studies of beta EEG utilizing the best-practices of genetic epidemiology.…”