Effect of Certain Genetic Variants in Nicotinic AChR on Substance Addictions: A Structural Equation Modeling Approach

Abstract

Abstract Nicotine addiction, like many other addictions, is a complex form of behavior with both genetic and environmental aspects. Although there is a need for studies investigating the interaction between environmental and genetic factors in the field of substance addiction, the number of studies that consider both aspects is limited. This study explored how certain genetic variants in the nicotine acetylcholine receptor (AChR) genes interact with nicotine and other types of substance addiction and environment. From the genetic data of 66936 variants, scores generated by Polygenic Risk Score (PRS) analysis for certain genetic variants found in nicotinic AChR genes. The relationship between this score and Wisconsin Index of Smoking Dependence Motives (WISDM), socio-economic status (SES), nicotine and other substance addictions was examined using structural equation modeling (SEM). The data set contains information of 2969 subjects (Female (1786) Male (1168)). PRS had a significant effect on the FTND as expected. PRS also showed a significant effect on alcohol addiction and marijuana addiction with higher coefficients than FTND. SES significantly affects WISDM. WISDM showed a significant effect on alcohol, marijuana, cocaine and opiate addiction. Thus, WISDM was examined as mediator of the relationship between SES and substance addictions. Alcohol addiction significantly affects nicotine, cocaine and marijuana addiction. These findings suggest that certain genetic variants in nicotinic AChR known to affect one type of addiction may also have an effect on other types of substance addictions. In addition, nicotinic AChR may be a clinically significant target for prevention of substance addictions other than nicotine.