Summary: Researchers have identified more than 500 genetic variants that influence tobacco and alcohol use, including aspects related to addiction and consumption patterns.
Source: University of Minnesota.
Tobacco and alcohol use are heritable behaviors that contribute substantially to mortality and raise the risk for many complex diseases and disorders.
The University of Minnesota participated in an international research collaboration that produced the first large-scale study to pinpoint hundreds of genomic regions linked to addictive behaviors. Published in Nature Genetics, the study analyzed genetic data from up to 1.2 million people and identified over 500 genetic variants associated with tobacco and alcohol use—far more than had been discovered previously.
Study design and measures
Researchers combined data from numerous cohorts to achieve a sample size of approximately 1.2 million individuals. They examined five primary behavioral measures related to tobacco and alcohol:
- Age at which a participant began smoking;
- Number of cigarettes smoked per day;
- Whether the participant ever became a regular smoker;
- Whether the participant ever quit smoking;
- Number of alcoholic drinks consumed per week.
Key findings
The study produced several important results that advance our understanding of the genetic architecture of substance use:
- Researchers discovered 566 genetic variants located in 406 genomic regions (loci) that are associated with stages of tobacco use—initiation, heaviness, and cessation—as well as alcohol use.
- One hundred fifty loci showed evidence of pleiotropy, meaning a single genomic region was associated with two or more of the measured behaviors.
- Higher genetic risk for smoking correlated with increased genetic risk for a variety of health conditions, including obesity and coronary artery disease.
- In contrast, genetic propensity for alcohol consumption was, on average, associated with lower genetic risk for some of these same health conditions in this analysis.
Biological insights and pathways
The analysis points to the involvement of multiple biological systems in substance use behaviors. Genes implicated include those involved in nicotinic signaling, dopaminergic pathways, and glutamatergic neurotransmission. These findings suggest that diverse molecular mechanisms contribute to initiation, consumption level, and cessation of tobacco and alcohol use.
Implications for research and treatment
According to Scott Vrieze, an associate professor in the Department of Psychology and a co-author on the project, these results provide a robust set of genetic loci to guide further work in model organisms and in studies that use more detailed substance-use measurements. The identified variants create opportunities to explore how genetic differences influence addiction biology and to inform development of targeted prevention and treatment strategies.
About the research
Funding: The study received support from the National Institute on Drug Abuse and the National Human Genome Research Institute, both components of the U.S. National Institutes of Health.
Source: University of Minnesota. Publisher: Organized by NeuroscienceNews.com. Image source: NeuroscienceNews.com image in the public domain.
Original research and citation
Original research article: “Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use” by Mengzhen Liu et al., published in Nature Genetics on January 14, 2019. DOI: 10.1038/s41588-018-0307-5.
Abstract (summary)
Tobacco and alcohol use are leading contributors to mortality and act as risk factors for many complex disorders. Both behaviors are heritable and have proven difficult targets for gene discovery until now. In a combined sample of up to 1.2 million people, investigators identified 566 genetic variants across 406 loci associated with different stages of tobacco use and with alcohol consumption, with 150 loci showing associations across multiple measures. Genetic correlations indicate that smoking-related traits are positively associated with numerous adverse health outcomes, whereas genetic predisposition to greater alcohol consumption showed negative correlations with those outcomes in this analysis. The findings implicate multiple neurotransmitter systems and provide a foundation for experimental follow-up and more precise phenotype measurement.
The discoveries reported here expand the catalog of genetic variants linked to substance use and establish a resource for future research into how genetic differences shape addiction risk and health trajectories.