Association between a 15q25 gene variant, nicotine-related habits, lung cancer and COPD among 56,307 individuals from the HUNT study in Norway

Eur J Hum Genet. 2013 Nov;21(11):1293-9. doi: 10.1038/ejhg.2013.26. Epub 2013 Feb 27.


Genetic studies have shown an association between single-nucleotide polymorphisms on chromosome 15q25 and smoking-related traits and diseases, such as quantity of smoking, lung cancer and chronic obstructive pulmonary disease (COPD). A discussion has centred on the variants and their effects being directly disease related or indirect via nicotine addiction. To address these discrepancies, we genotyped the single-nucleotide polymorphism rs16969968 in the CHRNA5/A3/B4 gene cluster at chromosome 15q25, in 56 307 individuals from a large homogenous population-based cohort, the North Trøndelag Health Study (HUNT) in Norway. The variant was examined in relation to four different outcomes: lung cancer, loss of lung function equivalent to that of COPD, smoking behaviour and the use of smokeless tobacco (snus). Novel associations were found between rs16969968 and the motivational factor for starting to use snus, and the quantity of snus used. Our results also confirm and extend previous findings for associations between rs16969968 and lung cancer, loss of lung function equivalent to that of COPD, and smoking quantity. Our data suggest a role for rs16969968 in nicotine addiction, and the novel association with snus strengthens this observation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Chromosomes, Human, Pair 15 / genetics*
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Humans
  • Lung / pathology
  • Lung / physiopathology
  • Lung Neoplasms / complications
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / physiopathology
  • Male
  • Middle Aged
  • Norway
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics
  • Proportional Hazards Models
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Smoking / genetics
  • Tobacco Use Disorder / complications
  • Tobacco Use Disorder / genetics*
  • Tobacco Use Disorder / physiopathology
  • Tobacco, Smokeless

Supplementary concepts

  • Pulmonary Disease, Chronic Obstructive, Severe Early-Onset