An international research team with members that include Yale scientist Marc Potenza, MD, PhD, have identified several genes and their variants that trigger both substance use and other potentially addictive behaviors.
The discovery not only underpins previous studies which showed that addiction could be genetically determined – but also indicates possible overlaps between different types of disorders influenced by the same genes.
Previous research has mostly focused on investigating possible relationships between genetic variants and one specific type of addiction. This study by researchers from Hungarian, British, American, and Gibraltarian universities examined a broad spectrum of substance and non-substance addictions and their possible associations with 32 gene polymorphisms (variants). The results have been published in the Journal of Personalized Medicine.
The genetic association analysis is part of the Psychological and Genetic Factors of Addictions (PGA) study assessing multiple addictive behaviours in 3003 young adults (the average age was 21). The researchers collected data at Hungarian high schools, colleges, and universities. All participants provided DNA samples and answered questionnaires.
They were asked about their alcohol consumption, tobacco, cannabis and other drug use, and their engagement in seven potentially addictive behaviours (internet use, gaming, social networking sites use, gambling, exercising, hair pulling, and eating). Participation was anonymous, and questionnaire data and DNA information were paired using a unique identification number for each participant.
"It has been previously proven that a strong genetic influence exists in case of different addictions. Heritability, which is the measure of genetic contribution to a trait, is estimated to be between 50 percent and 70 percent for addictions, and the rest is environmental effects,” said Dr. Csaba Barta, associate professor at the Department of Molecular Biology of Semmelweis University, Budapest, Hungary. “However, the specific genetic variants and their neurobiological roles in addiction are not so well known. We found 29 nominally significant associations in the current study, and nine of those remained significant after statistical correction for multiple testing."
The results showed that some genes and their variants could make a person susceptible to both the use of certain substances and also some other potentially addictive behaviours, which means that some people with these gene variants could have a predisposition to more than one type of addiction.
The researchers observed that one of the genes, FOXN3 and its so-called rs759364 A allele (variant), was associated with more frequent alcohol consumption. The same allele was also associated with a higher occurrence of problematic internet use and online gaming. In contrast, the carriers of the other, G allele were more prone to exercise addiction.
The team also found significant associations between the DRD2/ANKK1 gene and its so-called rs1800497 A allele and cannabis use.
The GDNF gene's rs1549250 and rs2973033 variants and the CNR1 gene's rs806380 variant showed associations with lifetime use of "other drugs" (other than cannabis).
"These findings can contribute to the scientific knowledge on addictions which affects millions of people worldwide,” said Dr. Zsolt Demetrovics, chair of the Centre of Excellence in Responsible Gaming at the University of Gibraltar and Professor of Psychology at Eötvös Loránd University, Budapest, Hungary. “A novelty of the PGA study is that it explores the relationships between substance use and non-substance-related addictive behaviours in detail. It could bring us closer to understanding the overlap between the vulnerability of different types of potentially addictive behaviours. For example, being vulnerable to problematic alcohol use might also pose an increased risk for gambling, video game use or working addiction. This could be a relevant consideration also when planning treatment interventions."
The PGA study is a major research project. The international scientific team has already published some other results from the data they gathered at the beginning of the work.
In one of the previous publications (2020), which focused on the epidemiological results, associations were found between smoking and problematic internet use, exercising, eating disorders, and gambling. The researchers observed a further connection between alcohol consumption and problematic internet use, online gaming, gambling, and eating disorders.
“The study provides support that some genetic factors may be responsible for the overlap we observed previously,” said Potenza, professor of psychiatry, in the Child Study Center and of neuroscience at Yale School of Medicine, and director of the Yale's Center of Excellence in Gambling Research. “Additional studies using larger samples and other analytic approaches (for example, genome-wide association studies) are needed to further substantiate these findings.”
The PGA study also found some interesting differences between genders concerning addictions. The lifetime occurrence of different types of drugs was significantly higher in males than females. However, sedatives were more often used by women than men. In the case of addictive behaviours, men were more prone to gambling, and more women than men were affected by eating disorders and excessive social media use.
The PGA team's next plan is to analyse the specific forms of addictions in more detail to disentangle more subtle correlations between gene variants and their effects on either alcohol use or smoking patterns.