Genetics and stem cells

Smoker’s genes

“Genes behind desire to smoke” is the headline in the Financial Times . Genetic differences may be the reason why some people who start smoking in their teens are hooked for life while others find it easier to quit, the newspaper says.

The complex genetic study behind this story has identified a particular cluster of genetic sequences that are more common in long-term smokers who start smoking before age 16 than in those who start after age 16. The identification of a group who are particularly susceptible to dependency raises the possibility of proactively targeting prevention efforts at groups who are most likely to benefit. However, such interventions are some way off. This study will be of particular interest to the scientific community and may precipitate further research to confirm these results in different populations.

Where did the story come from?

Dr Robert Weiss and colleagues from the University of Utah School of Medicine, the University of Wisconsin School of Medicine, the University of Minnesota and Salt Lake City VA Medical Center carried out this study. The work was funded by grants from the National Institutes of Health. It was published in the peer-reviewed medical journal: PLoS Genetics.

What kind of scientific study was this?

This study was a “candidate gene study”, a type of genetic case-control study, which looked at the associations between particular genetic variants in people who were either high or low dependence long-term smokers. Overall, the researchers were interested in exploring whether known variations in nicotine receptors are linked to nicotine dependence, and whether this relationship is dependent upon the age at which subjects started smoking (in adolescence or not).

The study had several different elements, one of which was a gene association study to identify particular sequences of gene variants (a group of genes so close together that they are inherited as a group) that are more commonly inherited in high-dependent long-term smokers than in low-dependent long-term smokers. The researchers combined data from three cohort studies across the USA that had recruited smokers or abstinent smokers: a study in Utah, a study in Wisconsin and the NHLBI Lung Health Study. The cohorts had different recruitment and entry criteria, and were composed of people of different ages and genders, with differing numbers of cigarettes smoked daily and different rates of smoking before age 16 years. However, they were similar in a measure of nicotine dependence (low or high dependence according to scores on the Fagerström Test of Nicotine Dependence). In total, 2,827 subjects were available for analysis.

In a subset of the total population – 144 participants who represented extreme heavy and extreme light dependency, as well as 48 non-smokers drawn from the population – the researchers identified variations in the genetic sequences that were different in the groups of ‘high-dependence’ and ‘low-dependence’ smokers. They then looked to see how significant these variants were in the larger sample of long-term smokers (2,827 smokers).

What were the results of the study?

The researchers found that a cluster of gene sequences – _CHRNA5-A3-B4 _ – are related to the severity of nicotine dependency (whether low or high dependence) in people who began daily smoking at or before age 16 years, but not in those who started smoking after age 16.

When they examined this particular cluster more carefully, the researchers found that one variation of it was associated with high dependence in those who started smoking before age 16, while another variation was associated with a protective effect in this group.

What interpretations did the researchers draw from these results?

The researchers conclude that the way in which gene variants are inherited in a particular cluster is linked to susceptibility to or protection from long-term nicotine dependency when age of exposure to cigarettes is considered. They say that being able to identify a “genetically high-risk” group such as this may help to proactively target public health interventions so that the population has a lower rate of adult nicotine addiction.

What does the NHS Knowledge Service make of this study?

This genetic study uses recognised methods to identify particular genetic sequences that differ between long-term smokers with high and low nicotine dependence.

  • As with other case-control study designs it is possible that there are other factors (in this case other parts of the genome) which could be associated with nicotine dependence. Larger studies involving more of the genetic sequence will be required to assess this.

The study does suggest that there may be a particular group of smokers who start smoking young who could be selectively targeted with preventative interventions. Such interventions are some way off, though this study will be of particular interest to the scientific community and may precipitate further research to confirm these results in different populations.

NHS Attribution