Whether or not you smoke can be influenced by heredity; new research may help identify specific risks, and ways to quit

Published 3:15 pm Friday, April 12, 2024

Kentucky Health News


If your parents or grandparents smoke, you are more likely to smoke. Perhaps that’s one reason smoking persists in Kentucky, which has had a higher rate of adult smoking than any state but West Virginia. 

“Smoking is highly heritable, with genetic differences accounting for 40% to 75% of the differences in people’s smoking behaviors,” says Pamela Romero Villela, a doctoral student at the University of Colorado and main author of a new study of the phenomenon.

The university’s Lisa Marshall writes, “Scientists have identified thousands of genetic variants believed to influence everything from when people first try smoking to how good that first cigarette feels to how often they light up and how hard it is to quit. Some variants influence how quickly we metabolize nicotine, while others underlie how sensitive we are to it. But little is known about how they interact with each other and with other genetic differences.”

The new study “sheds unprecedented light on these interactions and provides new insight on the most well-known smoking-related variant to date,” Marshall reports.

Romero Villela told Marshall, “The more we can understand what those genes do and how they interact, the better equipped we will be to develop personalized approaches to helping people quit.”

She and physiology Professor Marissa Ehringer, a longtime substance-use researcher, focused on the most widely replicated genetic variant associated with smoking behaviors, so important that researchers call it “Mr. Big.”

“Mr. Big . . . influences how well nicotine binds to receptors in the brain,” Marshall explains. “People with a certain version of Mr. Big, known as the AA version, are less sensitive to nicotine and have been shown to smoke more.”

Romero Villela rold her, “It kind of numbs your response so in order for you to feel the same effect as someone who smoked one cigarette you might have to smoke almost one and a half cigarettes.”

The researchers found something new “when analyzing genetic information from about 165,000 current or former smokers of European, South Asian and Finnish descent,” Marshall reports. “They discovered genes and variants in a completely different region of the genome that appear to interact with Mr. Big in a way that influences smoking habits. Notably, when people had the risk-boosting version of Mr. Big but also had a genetic variant called rs73586411, they smoked significantly less than expected.”

Marshall writes, “More research is needed to understand just what the genes highlighted in the study do. Interestingly, one . . . has previously been associated with Parkinson’s disease. Nicotine is known to blunt some symptoms of the disease.

“The study authors imagine a day when people could be given a ‘polygenic risk score’ that would consider their gene variants and interactions to provide personalized recommendations for quitting. . . . Eventually, if researchers could determine what a variant does to dull the craving to smoke, they might be able to develop medications that mimic that action.”

— Kentucky Health News is an independent news service of the Institute for Rural Journalism in the School of Journalism and Media at the University of Kentucky, with support from the Foundation for a Healthy Kentucky.