Mar. 27, 2013 Researchers have identified genetic risk factors that may accelerate a teen's progression to becoming a lifelong heavy smoker.

The team of scientists from the U.S., the U.K. and New Zealand examined earlier studies by other research teams to develop a genetic risk profile for heavy smoking. Then they looked at their own long-term study of 1,000 New Zealanders from birth to age 38 to identify whether individuals at high genetic risk got hooked on cigarettes more quickly as teens and whether, as adults, they had a harder time quitting.

Study participants who had the high-risk genetic profile were found to be more likely to convert to daily smoking as teenagers and then progress more rapidly to heavy smoking (a pack a day or more). When assessed at age 38, the higher-risk individuals had smoked heavily for more years, had more often developed nicotine dependence and were more likely to have failed in attempts to quit smoking.

"Genetic risk accelerated the development of smoking behavior," said Daniel Belsky, a post-doctoral research fellow at Duke University's Center for the Study of Aging and Human Development and the Duke Institute for Genome Sciences & Policy. "Teens at a high genetic risk transitioned quickly from trying cigarettes to becoming regular, heavy smokers."

A person's genetic risk profile did not predict whether he or she would try cigarettes. But for those who did try cigarettes, having a high-risk genetic profile predicted increased likelihood of heavy smoking and nicotine dependence.

The findings appear March 27 in JAMA Psychiatry. They were supported by multiple grants from the U.S. National Institutes of Health, as well as the U.K. Medical Research Council and the New Zealand Health Research Council.

The Duke researchers developed a new "genetic risk score" for the study by examining prior genome-wide associations (GWAS) of adult smokers. These studies scanned the entire genomes of tens of thousands of smokers to identify variants that were more common in the heaviest smokers. The variants they identified were located in and around genes that affect how the brain responds to nicotine and how nicotine is metabolized, but it is not yet known how the specific variants affect gene function.

It makes sense that the genes on which the group based their risk score are involved in nicotine metabolism and sensitivity, said Jed Rose, a Duke nicotine addiction researcher who was not involved in this study. "Addictions are a learned behavior and it requires reinforcement through neural pathways."

In their first step, the researchers found the genetic risk score they developed was able to predict heavy smoking among individuals in two large databases created by other researchers.

Then they turned to their New Zealand sample of 880 individuals of European descent to see whether the genetic risk score predicted who initiated smoking, who progressed to heavy smoking, and who developed nicotine dependence and experienced relapse after quitting.

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Genetics might determine which smokers get hooked

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