While some people smoke cigarettes casually for a short time and then quit, others have a long-term habit of smoking several packs per day. This risk of nicotine dependence appears to be a complex combination of genetic, environmental and behavioral factors.Research on twins suggests that between 40 and 70 percent of risk factors can be attributed to their parents. However, until recently, only 1% of observed variations in nicotine dependence liability could be explained by studies using a genetic score that is based on the number of cigarettes a person smokes each day.Emory University psychologists have created a new model to examine this genetic risk. The study used genome-wide association studies to examine a variety of traits and disorders that are correlated with nicotine dependence. It explained 3.6 percent variation in nicotine dependence.The finding was published in the journal Nicotine & Tobacco Research.The study revealed that higher polygenetic scores were associated with higher risks for schizophrenia, depression and neuroticism. They also indicate a greater risk of nicotine dependence. The results also showed that higher education earned polygenetic scores lowers the risk of nicotine dependence.Rohan Palmer, senior author of this study and assistant professor at Emory's Department of Psychology where he leads the Behavioral Genetics of Abdiction Laboratory, says, "If you look for the combined effect of all of those characteristics, our model accounts nearly 4 percent of variation in nicotine dependence. This is nearly four times more than what we learn when relying only on a genetic indicator for how many cigarettes someone smokes per day."Palmer says, "What we are finding is that genetic information can be used to enhance human potential and to make it more useful, we must look beyond individual traits and disorders to consider how different risk factors and traits interact." This broad approach can help us determine if someone is at high risk of developing a mental disorder such as nicotine dependence.Victoria Risner, Emory undergraduate majoring neuroscience and behavioral biology, adds that "all of the traits and diseases that we looked at were polygenic," and involves multiple genes. This means that there are likely to be millions of genetic variants that combine to create a complete picture of all the heritable nicotine dependence risks.Researchers hope others will continue to build on the multi-trait, complex genetic model and increase our understanding of these complex disorders. Palmer states that the more we know, the closer we are to having a genetic test that clinicians will be able to use to assess someone's nicotine dependence risk.Despite the fact that smoking is dangerous, only 14 percent of Americans smoke. The United States sees approximately 500,000 deaths each year from smoking and exposure to tobacco smoke. Another 16 million suffer from serious health problems caused by tobacco use. Although the harmful effects of smoking and vaping can be devastating to your health, the addictive nature of nicotine is what keeps people hooked.Risner was responsible for the current paper in her honors thesis. She says nicotine dependence was interesting because it was only a few years ago that the vaping industry was booming. "I noticed that some of my friends who were vaping became dependent on it quickly, while others who used the same products did not." "I was interested in the genetic underpinnings to this difference."This project used genome-wide association studies to study a variety of disorders and traits. Researchers then searched for matches in genetic data from a representative national sample of Americans with nicotine dependence. Results showed that the risk of developing dependence was affected by the polygenetic score for each disorder and trait. The most reliable predictors were the number of cigarettes smoked per days, self-perceived risk taking and educational attainment.Future studies will be guided by the multi-variant, polygenetic models. For example, adding risk associations (such nicotine metabolism) to the model may help reveal more information about nicotine dependence.Palmer states, "As we continue our efforts to identify who is most likely to become nicotine dependent and what inter-related factors (e.g genetic or environmental) may increase their risk, that could help us determine which intervention might be best for them."Risner states that it wasn't well known until a few decades back that nicotine dependence could be genetic. "Genetic studies could help decrease stigma society has about substance use disorders while making treatment more accessible."Risner graduated in 2019 from Emory and is currently enrolled in medical school at University of North Carolina, Chapel Hill. She'll be using the Emory coding and analysis skills to conduct research on genetic factors that could increase the risk of preterm births this summer.###Lauren Bertin, a graduate student at Emory, and Chelsie Benca–Bachman (post-doctoral fellow), are the co-authors of Nicotine & Tobacco Research article. Alicia Smith is an associate professor at the School of Medicine. Researchers from Brown University, the University of Helsinki, the Providence VA Medical Center, the Jackson Laboratory in Bar Harbor (Maine), Purdue University and the University of Colorado Boulder are also included.The National Institute on Drug Abuse funded the work on the Nicotine & Tobacco Research Article.
