A variant associated with nicotine dependence, lung cancer and peripheral arterial disease by Thorgeirsson Thorgeir E, 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, Gotts├Ąter 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, Stefansson Kari in Nature (2008).

[PMID: 18385739] PubMed


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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