Genetics may determine who becomes a heavy smoker

Individuals who pick up smoking as teenagers have a much higher risk of becoming heavy smokers as adults.  And for some, the risk is even greater – depending on their genetics.

A team of researchers from the United States, the U.K. and New Zealand utilized previous research on genetics and smoking to develop a genetic risk profile for individuals who eventually become heavy smokers.

The research revealed  individuals with a high-genetic risk for smoking were much more likely to become heavy smokers as adults, but only if they had tried cigarettes as teenagers.  Those who were determined to have low-genetic risk were much less likely to progress into heavy smoking, even if they had tried cigarettes when they were younger.

“Smoking behavior is a major public health problem, which develops relatively early in life,” lead author Dan Belsky, a post-doctoral research fellow at Duke University’s Center for the Study of Aging and Human Development, told  “We know from studies in families that genetics makes a difference in who becomes hooked on cigarettes and who doesn’t.  Relatives who share more genes are more similar in their smoking behavior.”

"(Genetics) didn't predict who tried cigarettes, but they did tell you who among those that did try a cigarette – who got hooked."

— Dan Belsky, lead author for the study

Belsky noted their research was based on large genome-wide association studies (GWAS) from 2010 on smoking behavior, in which scientists looked across entire genomes to identify variants linked with heavy smoking. Those studies identified variants in single nucleotide polymorphisms located in and around two groups of genes – the nicotine receptor genes, which control how the brain responds to nicotine, and the CYP2A6 region, which is responsible for nicotine metabolism in the liver.

What the studies did not show was when these genetic risks first manifest.  Belsky and his team also wanted to know if early manifestation of these genetic risk factors were critical to the genetic influence on adult smoking problems.

To better understand how these genetic variations influence behavior, the scientists followed 1,000 New Zealanders from birth to the age of 38, analyzing their smoking habits in relation to their known genetic risk.  Utilizing the genetic risk score developed to predict heavy smoking among individuals, the researchers cross analyzed an individual’s risk score with their smoking habits throughout the course of the lives.

Pack-a-day by 18

Ultimately, the results showed that genetic risk was best at predicting whether or not a teenager who tried cigarettes grew to become a heavy smoker.

“We found that these genetic differences do emerge during adolescence,” Belsky said.  “They didn’t predict who tried cigarettes, but they did tell you who among those that did try a cigarette – who got hooked.”

Out of the study participants, 70 percent tried cigarettes during their teenage years.  Among the teens who tried cigarettes, those with high genetic risk were 24 percent more likely to become daily smokers by the age of 15, and 43 percent were more likely to become pack-a-day smokers by the age of 18.

On average, those with a high-risk genetic profile had smoked 7,300 cigarettes more than the average smoker by the time they had reached the age 38.
However, a person’s genetic profile only seemed to be poignant if the individual tried cigarettes in his or her youth.  If the high-risk person did not try smoking in their teens, they became “immune” to their genetic risk for becoming a heavy adult smoker.  Therefore, if a high-risk person waited long enough, they were in the clear.

“In general, our findings argue for the importance of interventions and policies that prevent teens from becoming regular smokers,” Belsky said.  “It is easier to stop someone form initiating smoking behavior; that’s cheaper than helping them quit smoking.”

Belsky added that individuals with high-risk genetics were 22 percent more likely to fail at their attempts to quit smoking than those with low-risk profiles.

Belsky said their study’s findings point to the significance of teenage intervention when it comes to establishing anti-smoking behavior.  In terms of using genetic profiling to determine an individual’s personal risk of becoming a smoker, Belsky said it’s not quite time for that yet.

“I wouldn’t recommend using it for personalized medicine just yet, just because (genetic profiling) hasn’t fully been fleshed out yet,” Belsky said.  “However, we have found genetic factors make a big difference, and using genetics to make these predications may be possible in the future.”

The study was published in JAMA Psychiatry.