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

• Published in: Nature Vol. 452; no. 7187; pp. 638 - 642
• Main Authors: Thorgeirsson, Thorgeir E, Stefansson, Kari, Geller, Frank, Sulem, Patrick, Rafnar, Thorunn, Wiste, Anna, Magnusson, Kristinn P, Manolescu, Andrei, Thorleifsson, Gudmar, Stefansson, Hreinn, Ingason, Andres, Stacey, Simon N, Bergthorsson, Jon T, Thorlacius, Steinunn, Gudmundsson, Julius, Jonsson, Thorlakur, Jakobsdottir, Margret, Saemundsdottir, Jona, Olafsdottir, Olof, Gudmundsson, Larus J, Bjornsdottir, Gyda, Kristjansson, Kristleifur, Skuladottir, Halla, Isaksson, Helgi J, Gudbjartsson, Tomas, Jones, Gregory T, Mueller, Thomas, Gottsäter, Anders, Flex, Andrea, Aben, Katja K. H, de Vegt, Femmie, Mulders, Peter F. A, Isla, Dolores, Vidal, Maria J, Asin, Laura, Saez, Berta, Murillo, Laura, Blondal, Thorsteinn, Kolbeinsson, Halldor, Stefansson, Jon G, Hansdottir, Ingunn, Runarsdottir, Valgerdur, Pola, Roberto, Lindblad, Bengt, van Rij, Andre M, Dieplinger, Benjamin, Haltmayer, Meinhard, Mayordomo, Jose I, Kiemeney, Lambertus A, Matthiasson, Stefan E, Oskarsson, Hogni, Tyrfingsson, Thorarinn, Gudbjartsson, Daniel F, Gulcher, Jeffrey R, Jonsson, Steinn, Thorsteinsdottir, Unnur, Kong, Augustine
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.04.2008; Nature Publishing; Nature Publishing Group
• Subjects: Addictions; Biological and medical sciences; Blood and lymphatic vessels; Cardiac and Cardiovascular Systems; Cardiology. Vascular system; Case studies; Chromosomes, Human, Pair 15 - genetics; Cigarettes; Clinical Medicine; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Europe; Female; Genetic Predisposition to Disease - genetics; Genomics; Genotype; Genotype-environment interactions; Humanities and Social Sciences; Humans; Kardiologi; Klinisk medicin; letter; Lung cancer; Lung Neoplasms - genetics; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; multidisciplinary; Multigene Family - genetics; New Zealand; Nicotine; Odds Ratio; Pathology; Peripheral Vascular Diseases - genetics; Pneumology; Polymorphism, Single Nucleotide - genetics; Preventable deaths; Public health; Receptors, Nicotinic - genetics; Risk factors; Science; Science (multidisciplinary); Smoking; Smoking - adverse effects; Smoking - genetics; Tobacco Use Disorder - genetics; Tumors of the respiratory system and mediastinum; Netherlands; Atlantic Ocean Islands; Europe; Iceland; Spain; New Zealand; Human; Lung disease; Genetic variability; Respiratory disease; Lung cancer; Tobacco smoking; Cardiovascular disease; Genotype; Malignant tumor; Epidemiology; Arterial disease; Vascular disease; Alkaloid; Cholinergic receptor; Cancerology; Risk factor; Genetics; Bronchus disease; Occlusive arterial disease; Nicotinic receptor; Public health; Cancer; Nicotine
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature06846

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.