Joelle van Rijswijk-Pasman
Genetic and environmental risk factors for substance use
Twin studies have shown that addictive behaviour is heritable, with results suggesting that up to 75% of the variance in substance use and addiction is explained through heritability. However, the effect of individual genetic factors is very small, regardless of the study method used. This problem of ‘missing heritability’ may in part be explained through the neglect of environmental variables in those studies, and more specifically, through the neglect of interaction between those variables and genetic predisposition (genetic x environment interaction, or GxE).
The methodological focus of this project is to explore genetic and environmental factors in substance (ab)use, and especially the interaction between the two, using novel methods aimed at increasing power. Several innovative approaches will be used, including the combining of alleles of a candidate pathway (dopaminergic pathway) in an aggregate genetic risk score. Another approach is the use of polygenic risk scores based on large genetic consortia. Also, genome-wide association (GWA) may shed light on the relation between genotype and substance use. Mechanistic accounts of genetic risk will be explored using moderation and mediation models, wherein the relative importance of specific genetic and environmental risk may also become more clear.
People who are addicted to a specific substance often use other substances too. This phenomenon is called ‘poly-substance use’. With several methods (twin studies, polygenic risk scores and LD score regression) it has been shown that there is overlap between the genetic factors that influence nicotine, alcohol and illicit drug use. Therefore the current project will focus on the concurrent use of several substances (=poly-substance use) at the same time, or multiple substances during lifetime (= substance use behaviour). The research will include use and abuse of nicotine, alcohol, cannabis, and other illicit drugs.
|Prof. Jacqueline Vink, dr. Karin Verweij|