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Nature. 2008 Apr 3;452(7187):638-642. doi: 10.1038/nature06846.

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

Author information

1
deCODE Genetics, Reykjavik Iceland.
2
Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, GA US.
3
Landspitali University Hospital, Department of Medical Oncology, Reykjavik Iceland.
4
Landspitali University Hospital, Department of Pathology, Reykjavik Iceland.
5
Landspitali University Hospital, Department of Cardiothoracic Surgery, Reykjavik Iceland.
6
Department of Surgery, Dunedin School of Medicine, University of Otago, New Zealand.
7
Department of Laboratory Medicine, Konventhospital Barmherzige Brueder, Linz, Austria.
8
Center for Vascular Diseases, University Hospital. MAS, Malmö, Sweden.
9
Laboratory of Vascular Biology & Genetics, A. Gemelli University Hospital,Universita Cattolica del Sacro Cuore School of Medicine, Rome, Italy.
10
Radboud University Nijmegen Medical Centre, Department of Epidemiology & Biostatistics, Nijmegen, Netherlands.
11
Comprehensive Cancer Center East, Nijmegen, Netherlands.
12
Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, Netherlands.
13
University Hospital, Division of Medical Oncology, Zaragoza Spain.
14
Nanotechnology Institute of Aragon, Zaragoza Spain.
15
Health Science Institute, Zaragoza Spain.
16
Hospital Reina Sofia, Division of Medical Oncology, Tudela Spain.
17
Reykjavik Primary Health Care Centre, Department of Lung Disease, Reykjavik Iceland.
18
Landspitali University Hospital, Department of General Adult Psychiatry, Reykjavik Iceland.
19
Vogur SAA Addiction Treatment Center, Reykjavik Iceland.
20
University of Iceland, School of Medicine, Reykjavik Iceland.
21
Therapeia, Reykjavik Iceland.
22
Landspitali University Hospital, Department of Medicine, Reykjavik Iceland.
#
Contributed equally

Abstract

Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). 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 genome-wide association study that used low-quantity smokers as controls, 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, highlighting the role of nicotine addiction in the pathology of other serious diseases.

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PMID:
18385739
PMCID:
PMC4539558
DOI:
10.1038/nature06846
[Indexed for MEDLINE]
Free PMC Article
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