A systematic review of gene-by-intervention studies of alcohol and other substance use

Abstract

Alcohol and other substance use problems are common, and the efficacy of current prevention and intervention programs is limited. Genetics may contribute to differential effectiveness of psychosocial prevention and intervention programs. This paper reviews gene-by-intervention (G×I) studies of alcohol and other substance use, and implications for integrating genetics into prevention science. Systematic review yielded 17 studies for inclusion. Most studies focused on youth substance prevention, alcohol was the most common outcome, and measures of genotype were heterogeneous. All studies reported at least one significant G×I interaction. We discuss these findings in the context of the history and current state of genetics, and provide recommendations for future G×I research. These include the integration of genome-wide polygenic scores into prevention studies, broad outcome measurement, recruitment of underrepresented populations, testing mediators of G×I effects, and addressing ethical implications. Integrating genetic research into prevention science, and training researchers to work fluidly across these fields, will enhance our ability to determine the best intervention for each individual across development. With growing public interest in obtaining personalized genetic information, we anticipate that the integration of genetics and prevention science will become increasingly important as we move into the era of precision medicine.

Association between genetic risk of alcohol consumption and alcohol‐related morbidity and mortality under different alcohol policy conditions: Evidence from the Finnish alcohol price reduction of 2004

“…The analysis thus did not confirm the hypothesis of a 'diathesis-stress'-type interaction found in several previous studies [7][8][9][10][11],…”

“…Previous twin and molecular genetic studies investigating alcohol‐related gene–environment interactions with other environmental exposures have found that environments with more social control, for example in the form of romantic partnerships [7], religious [8] or rural communities [9] and adolescent peer groups [10], attenuate the association between genetic susceptibility and alcohol use or the heritability of alcohol use. Furthermore, those with high genetic susceptibility may gain disproportionate benefits from targeted interventions such as health education or therapy [11]. These results give support to the ‘diathesis–stress’ model of gene–environment interactions, implying that when alcohol becomes less expensive and/or easier to acquire, genetic influences may become more pronounced [12–15].…”

Developmental behavioral genetics research on school achievement is missing vulnerable children, to our detriment

“…Certainly, many gene‐by‐environment interaction models are correlational and do not allow causative conclusions (and some are prone to problems, van der Sluis et al., 2012, and some are simply wrong and should not be used, e.g., Duncan & Keller, 2011), however they begin to give us evidence to allow us to characterize groups of individuals who may be vulnerable for school difficulties based on environmental factors. Newer approaches to gene‐by‐environment interaction models, which include using genomic data and randomized controlled trial methods, can help us understand for whom and when an environmental intervention works or what environments matter the most (e.g., Burgoyne et al., 2020; Harden & Koellinger, 2020; Neale et al., 2021). These newer variations of gene‐by‐environmental interactions are very powerful in understanding the causal role of the environment (e.g., Neale et al., 2021).…”

“…Newer approaches to gene‐by‐environment interaction models, which include using genomic data and randomized controlled trial methods, can help us understand for whom and when an environmental intervention works or what environments matter the most (e.g., Burgoyne et al., 2020; Harden & Koellinger, 2020; Neale et al., 2021). These newer variations of gene‐by‐environmental interactions are very powerful in understanding the causal role of the environment (e.g., Neale et al., 2021).…”

Genetic moderation of the effects of family‐focused interventions (GxI interaction): A systematic review

“…van Ijzendoorn and Bakermans‐Kranenburg (2015) conducted a meta‐analysis to examine the magnitudes of GxI interaction effects from 22 psychosocial, behavioral, and cognitive intervention studies. The other review primarily focused on alcohol and substance use as the outcome of interest (Neale et al, 2020).…”