New genetic links found to heavy smoking and lung disease

Researchers have found five new genetic variants associated with heavy smoking and six new variants associated with lung health and chronic obstructive pulmonary disease (COPD), by using over 50,000 samples from the UK Biobank. The authors of the study, published in The Lancet Respiratory Medicine, say their findings help improve understanding of smoking behavior and lung diseases, and could open new ways to prevent nicotine addiction and manage disease. 

Dr. David Cutler, Assistant Professor, Department of Human Genetics, Emory University (webpage):

Expertise: population genetics applications to human disease studies, analyzing whole genome data sets to discover genetic variants associated with disease.

“This is a smart, well designed study that examines two related but separable questions. One, are genetic variants associated with lung function and health (COPD) independent of smoking behavior, and two, are genetic variants associated with smoking behavior independent of overall lung function. The authors can answer both questions simultaneously because of a very careful design that contained large numbers of individuals from all categories.

“The answer to both questions turns out to be yes, but honestly we knew the answer was yes before this study. There are almost always genetic effects that can be detected in a sufficiently large and well-designed study. This study has found a few previously unknown genes associated with both lung function (independent of smoking), and smoking decisions (independent of lung function). However, all the variants found have a very, very weak effect. Together they account for only a tiny fraction of the variance of either lung function or smoking decisions. The largest effect variants together explain well less than 1% of either COPD or smoking behavior. This is typical of most well designed studies of humans and similar to most other phenotypes studied by others, the particular effects detected here are very small individually.  

“We have known for ~5 years that genetic variation in one of the brain receptors with which nicotine interacts (the nicotinic receptor) is weakly associated with individuals’ decisions to smoke. Even this well-known genetic variation explains well less than 1% of the variation in whether or not people smoke. This study, in fact, does a superb job of showing that the effect of the nicotinic receptor is real, but remarkably small. This is an excellent piece of science, carefully done, but the magnitude of the effects found are quite weak.”


Dr. Kristina Allen-Brady, Research Assistant Professor, Genetic Epidemiology Division, Department of Internal Medicine, University of Utah (webpage):

Expertise: genetic epidemiology, public health, development of new methods to analyze genetic data

“Chronic obstructive pulmonary disease (COPD) is a complex disease in which multiple genes and environmental factors interact with each other.  In this study the team identified six new genetic variants associated with air flow obstruction, measured by the volume of air exhaled in a forced breath in 1 second or FEV1  and also COPD.  Five of these variants were associated with FEV1 in never smokers and also in heavy smokers.  The study team also identified five new genetic variants related to smoking behavior and addiction.

“While the news of finding additional genetic variants that contribute to COPD is exciting, the study team reported that 26 previously published genetic variants for lung function explain only 2.33% of the variation in FEV1 between individuals.  Adding in these six new genetic variants into the mathematical model explains 3.63% of the variation in FEV1. To put these numbers in perspective, previous mathematical models have shown that smoking accounts for approximately 15% of the variation in FEV1 (Beck et. al., Am Rev Respir Dis. 1981).  Much of the variation of COPD remains to be explained, even with the addition of these six new genetic variants.

“For smoking behavior, each of the five genetic variants associated was also found to contribute a very small percentage to the overall risk of smoking.

“The study results are likely valid.  The study involved a large sample of 50,000 subjects with European ancestry with lung function tests available. They sampled extremes of FEV1 (low, average, and high) in both heavy smokers and never smokers.  Although the study results have not yet been replicated by other researchers, the study team observed that some of the results were similar for both never smokers and heavy smokers.”


Declared interests (see GENeS register of interests policy):

No interests declared



Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank‘ by Louise V Wain et. al., published in The Lancet Respiratory Medicine on Sunday 27 September 2015.


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