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

@article{citeulike:2624227, 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.}, 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 Gotts\"{a}ter, Anders and Flex, Andrea and Aben, Katja K. and de Vegt, Femmie and Mulders, Peter F. 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}, citeulike-article-id = {2624227}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature06846}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature06846}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18385739}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18385739}, day = {3}, doi = {10.1038/nature06846}, issn = {1476-4687}, journal = {Nature}, keywords = {addiction, association, lungcancer}, month = {April}, number = {7187}, pages = {638--642}, posted-at = {2009-10-19 21:45:12}, priority = {2}, publisher = {Nature Publishing Group}, 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} }

TY - JOUR ID - citeulike:2624227 L3 - citeulike-article-id:2624227 N2 - 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. IS - 7187 JF - Nature SN - 1476-4687 EP - 642 TI - A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. PB - Nature Publishing Group VL - 452 SP - 638 KW - addiction KW - association KW - lungcancer AU - Thorgeirsson, Thorgeir AU - Geller, Frank AU - Sulem, Patrick AU - Rafnar, Thorunn AU - Wiste, Anna AU - Magnusson, Kristinn AU - Manolescu, Andrei AU - Thorleifsson, Gudmar AU - Stefansson, Hreinn AU - Ingason, Andres AU - Stacey, Simon AU - Bergthorsson, Jon AU - Thorlacius, Steinunn AU - Gudmundsson, Julius AU - Jonsson, Thorlakur AU - Jakobsdottir, Margret AU - Saemundsdottir, Jona AU - Olafsdottir, Olof AU - Gudmundsson, Larus AU - Bjornsdottir, Gyda AU - Kristjansson, Kristleifur AU - Skuladottir, Halla AU - Isaksson, Helgi AU - Gudbjartsson, Tomas AU - Jones, Gregory AU - Mueller, Thomas AU - Gottsäter, Anders AU - Flex, Andrea AU - Aben, Katja AU - de Vegt, Femmie AU - Mulders, Peter AU - Isla, Dolores AU - Vidal, Maria AU - Asin, Laura AU - Saez, Berta AU - Murillo, Laura AU - Blondal, Thorsteinn AU - Kolbeinsson, Halldor AU - Stefansson, Jon AU - Hansdottir, Ingunn AU - Runarsdottir, Valgerdur AU - Pola, Roberto AU - Lindblad, Bengt AU - van Rij, Andre AU - Dieplinger, Benjamin AU - Haltmayer, Meinhard AU - Mayordomo, Jose AU - Kiemeney, Lambertus AU - Matthiasson, Stefan AU - Oskarsson, Hogni AU - Tyrfingsson, Thorarinn AU - Gudbjartsson, Daniel AU - Gulcher, Jeffrey AU - Jonsson, Steinn AU - Thorsteinsdottir, Unnur AU - Kong, Augustine AU - Stefansson, Kari PY - 2008/04/03/ UR - http://dx.doi.org/10.1038/nature06846 ER -