FOXN3 and GDNF Polymorphisms as Common Genetic Factors of Substance Use and Addictive Behaviors

Epidemiological and phenomenological studies suggest shared underpinnings between multiple addictive behaviors. The present genetic association study was conducted as part of the Psychological and Genetic Factors of Addictions study (n = 3003) and aimed to investigate genetic overlaps between different substance use, addictive, and other compulsive behaviors. Association analyses targeted 32 single-nucleotide polymorphisms, potentially addictive substances (alcohol, tobacco, cannabis, and other drugs), and potentially addictive or compulsive behaviors (internet use, gaming, social networking site use, gambling, exercise, hair-pulling, and eating). Analyses revealed 29 nominally significant associations, from which, nine survived an FDRb1 correction. Four associations were observed between FOXN3 rs759364 and potentially addictive behaviors: rs759364 showed an association with the frequency of alcohol consumption and mean scores of scales assessing internet addiction, gaming disorder, and exercise addiction. Significant associations were found between GDNF rs1549250, rs2973033, CNR1 rs806380, DRD2/ANKK1 rs1800497 variants, and the "lifetime other drugs" variable. These suggested that genetic factors may contribute similarly to specific substance use and addictive behaviors. Specifically, FOXN3 rs759364 and GDNF rs1549250 and rs2973033 may constitute genetic risk factors for multiple addictive behaviors. Due to limitations (e.g., convenience sampling, lack of structured scales for substance use), further studies are needed. Functional correlates and mechanisms underlying these relationships should also be investigated.