A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.
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.
Thorgeirsson
Thorgeir E
TE
deCODE Genetics, Reykjavik Iceland.
Geller
Frank
F
deCODE Genetics, Reykjavik Iceland.
Sulem
Patrick
P
deCODE Genetics, Reykjavik Iceland.
Rafnar
Thorunn
T
deCODE Genetics, Reykjavik Iceland.
Wiste
Anna
A
deCODE Genetics, Reykjavik Iceland.|Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, GA US.
Magnusson
Kristinn P
KP
deCODE Genetics, Reykjavik Iceland.
Manolescu
Andrei
A
deCODE Genetics, Reykjavik Iceland.
Thorleifsson
Gudmar
G
deCODE Genetics, Reykjavik Iceland.
Stefansson
Hreinn
H
deCODE Genetics, Reykjavik Iceland.
Ingason
Andres
A
deCODE Genetics, Reykjavik Iceland.
Stacey
Simon N
SN
deCODE Genetics, Reykjavik Iceland.
Bergthorsson
Jon T
JT
deCODE Genetics, Reykjavik Iceland.
Thorlacius
Steinunn
S
deCODE Genetics, Reykjavik Iceland.
Gudmundsson
Julius
J
deCODE Genetics, Reykjavik Iceland.
Jonsson
Thorlakur
T
deCODE Genetics, Reykjavik Iceland.
Jakobsdottir
Margret
M
deCODE Genetics, Reykjavik Iceland.
Saemundsdottir
Jona
J
deCODE Genetics, Reykjavik Iceland.
Olafsdottir
Olof
O
deCODE Genetics, Reykjavik Iceland.
Gudmundsson
Larus J
LJ
deCODE Genetics, Reykjavik Iceland.
Bjornsdottir
Gyda
G
deCODE Genetics, Reykjavik Iceland.
Kristjansson
Kristleifur
K
deCODE Genetics, Reykjavik Iceland.
Skuladottir
Halla
H
Landspitali University Hospital, Department of Medical Oncology, Reykjavik Iceland.
Isaksson
Helgi J
HJ
Landspitali University Hospital, Department of Pathology, Reykjavik Iceland.
Gudbjartsson
Tomas
T
Landspitali University Hospital, Department of Cardiothoracic Surgery, Reykjavik Iceland.
Jones
Gregory T
GT
Department of Surgery, Dunedin School of Medicine, University of Otago, New Zealand.
Mueller
Thomas
T
Department of Laboratory Medicine, Konventhospital Barmherzige Brueder, Linz, Austria.
Gottsäter
Anders
A
Center for Vascular Diseases, University Hospital. MAS, Malmö, Sweden.
Flex
Andrea
A
Laboratory of Vascular Biology & Genetics, A. Gemelli University Hospital,Universita Cattolica del Sacro Cuore School of Medicine, Rome, Italy.
Aben
Katja K H
KKH
Radboud University Nijmegen Medical Centre, Department of Epidemiology & Biostatistics, Nijmegen, Netherlands.|Comprehensive Cancer Center East, Nijmegen, Netherlands.
de Vegt
Femmie
F
Radboud University Nijmegen Medical Centre, Department of Epidemiology & Biostatistics, Nijmegen, Netherlands.
Mulders
Peter F A
PFA
Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, Netherlands.
Isla
Dolores
D
University Hospital, Division of Medical Oncology, Zaragoza Spain.
Vidal
Maria J
MJ
University Hospital, Division of Medical Oncology, Zaragoza Spain.
Asin
Laura
L
Nanotechnology Institute of Aragon, Zaragoza Spain.
Saez
Berta
B
Health Science Institute, Zaragoza Spain.
Murillo
Laura
L
Hospital Reina Sofia, Division of Medical Oncology, Tudela Spain.
Blondal
Thorsteinn
T
Reykjavik Primary Health Care Centre, Department of Lung Disease, Reykjavik Iceland.
Kolbeinsson
Halldor
H
Landspitali University Hospital, Department of General Adult Psychiatry, Reykjavik Iceland.
Stefansson
Jon G
JG
Landspitali University Hospital, Department of General Adult Psychiatry, Reykjavik Iceland.
Hansdottir
Ingunn
I
Vogur SAA Addiction Treatment Center, Reykjavik Iceland.
Runarsdottir
Valgerdur
V
Vogur SAA Addiction Treatment Center, Reykjavik Iceland.
Pola
Roberto
R
Laboratory of Vascular Biology & Genetics, A. Gemelli University Hospital,Universita Cattolica del Sacro Cuore School of Medicine, Rome, Italy.
Lindblad
Bengt
B
Center for Vascular Diseases, University Hospital. MAS, Malmö, Sweden.
van Rij
Andre M
AM
Department of Surgery, Dunedin School of Medicine, University of Otago, New Zealand.
Dieplinger
Benjamin
B
Department of Laboratory Medicine, Konventhospital Barmherzige Brueder, Linz, Austria.
Haltmayer
Meinhard
M
Department of Laboratory Medicine, Konventhospital Barmherzige Brueder, Linz, Austria.
Mayordomo
Jose I
JI
University Hospital, Division of Medical Oncology, Zaragoza Spain.|Nanotechnology Institute of Aragon, Zaragoza Spain.|Health Science Institute, Zaragoza Spain.
Kiemeney
Lambertus A
LA
Radboud University Nijmegen Medical Centre, Department of Epidemiology & Biostatistics, Nijmegen, Netherlands.|Comprehensive Cancer Center East, Nijmegen, Netherlands.|Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, Netherlands.
Matthiasson
Stefan E
SE
University of Iceland, School of Medicine, Reykjavik Iceland.
Oskarsson
Hogni
H
Therapeia, Reykjavik Iceland.
Tyrfingsson
Thorarinn
T
Vogur SAA Addiction Treatment Center, Reykjavik Iceland.
Gudbjartsson
Daniel F
DF
deCODE Genetics, Reykjavik Iceland.
Gulcher
Jeffrey R
JR
deCODE Genetics, Reykjavik Iceland.
Jonsson
Steinn
S
Landspitali University Hospital, Department of Medicine, Reykjavik Iceland.
Thorsteinsdottir
Unnur
U
deCODE Genetics, Reykjavik Iceland.|University of Iceland, School of Medicine, Reykjavik Iceland.
Kong
Augustine
A
deCODE Genetics, Reykjavik Iceland.
Stefansson
Kari
K
deCODE Genetics, Reykjavik Iceland.|University of Iceland, School of Medicine, Reykjavik Iceland.
D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D005810:Multigene Family / Q000235:genetics; D009520:New Zealand; D016017:Odds Ratio; D016491:Peripheral Vascular Diseases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects / Q000235:genetics; D014029:Tobacco Use Disorder / Q000235:genetics*
D011978:Receptors, Nicotinic