Advanced

A variant associated with nicotine dependence, lung cancer and peripheral arterial disease

Thorgeirsson, Thorgeir E; Geller, Frank; Sulem, Patrick; Rafnar, Thorunn; Wiste, Anna; Magnusson, Kristinn P; Manolescu, Andrei; Thorleifsson, Gudmar; Stefansson, Hreinn and Ingason, Andres, et al. (2008) In Nature 452(7187). p.9-638
Abstract
Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year(1,2). Evidence for genetic influence on smoking behaviour and nicotine dependence (ND)(3-8) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health(9,10). Smoking is the major risk factor for lung cancer (LC)(11-14) and is one of the main risk factors for peripheral arterial disease (PAD)(15-17). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking- related diseases in populations of European descent. The... (More)
Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year(1,2). Evidence for genetic influence on smoking behaviour and nicotine dependence (ND)(3-8) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health(9,10). Smoking is the major risk factor for lung cancer (LC)(11-14) and is one of the main risk factors for peripheral arterial disease (PAD)(15-17). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking- related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genomewide association study that used low- quantity smokers as controls(18,19), and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene - environment interaction(20), highlighting the role of nicotine addiction in the pathology of other serious diseases. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature
volume
452
issue
7187
pages
9 - 638
publisher
Nature Publishing Group
external identifiers
  • wos:000254567200047
  • scopus:41649103052
ISSN
0028-0836
DOI
10.1038/nature06846
language
English
LU publication?
yes
id
727d67c9-3721-44c6-9c2b-d55423cf5a22 (old id 1182882)
date added to LUP
2008-09-02 09:39:56
date last changed
2017-11-19 03:37:09
@article{727d67c9-3721-44c6-9c2b-d55423cf5a22,
  abstract     = {Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year(1,2). Evidence for genetic influence on smoking behaviour and nicotine dependence (ND)(3-8) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health(9,10). Smoking is the major risk factor for lung cancer (LC)(11-14) and is one of the main risk factors for peripheral arterial disease (PAD)(15-17). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking- related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genomewide association study that used low- quantity smokers as controls(18,19), and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene - environment interaction(20), highlighting the role of nicotine addiction in the pathology of other serious diseases.},
  author       = {Thorgeirsson, Thorgeir E and Geller, Frank and Sulem, Patrick and Rafnar, Thorunn and Wiste, Anna and Magnusson, Kristinn P and Manolescu, Andrei and Thorleifsson, Gudmar and Stefansson, Hreinn and Ingason, Andres and Stacey, Simon N and Bergthorsson, Jon T and Thorlacius, Steinunn and Gudmundsson, Julius and Jonsson, Thorlakur and Jakobsdottir, Margret and Saemundsdottir, Jona and Olafsdottir, Olof and Gudmundsson, Larus J and Bjornsdottir, Gyda and Kristjansson, Kristleifur and Skuladottir, Halla and Isaksson, Helgi J and Gudbjartsson, Tomas and Jones, Gregory T and Mueller, Thomas and Gottsäter, Anders and Flex, Andrea and Aben, Katja K H and de Vegt, Femmie and Mulders, Peter F A and Isla, Dolores and Vidal, Maria J and Asin, Laura and Saez, Berta and Murillo, Laura and Blondal, Thorsteinn and Kolbeinsson, Halldor and Stefansson, Jon G and Hansdottir, Ingunn and Runarsdottir, Valgerdur and Pola, Roberto and Lindblad, Bengt and van Rij, Andre M and Dieplinger, Benjamin and Haltmayer, Meinhard and Mayordomo, Jose I and Kiemeney, Lambertus A and Matthiasson, Stefan E and Oskarsson, Hogni and Tyrfingsson, Thorarinn and Gudbjartsson, Daniel F and Gulcher, Jeffrey R and Jonsson, Steinn and Thorsteinsdottir, Unnur and Kong, Augustine and Stefansson, Kari},
  issn         = {0028-0836},
  language     = {eng},
  number       = {7187},
  pages        = {9--638},
  publisher    = {Nature Publishing Group},
  series       = {Nature},
  title        = {A variant associated with nicotine dependence, lung cancer and peripheral arterial disease},
  url          = {http://dx.doi.org/10.1038/nature06846},
  volume       = {452},
  year         = {2008},
}