A variant associated with nicotine dependence, lung cancer and peripheral arterial disease
Thorgeir E Thorgeirsson, Frank Geller, Patrick Sulem, Thorunn Rafnar, Anna Wiste, Kristinn P Magnusson, Andrei Manolescu, Gudmar Thorleifsson, Hreinn Stefansson, Andres Ingason, Simon N Stacey, Jon T Bergthorsson, Steinunn Thorlacius, Julius Gudmundsson, Thorlakur Jonsson, Margret Jakobsdottir, Jona Saemundsdottir, Olof Olafsdottir, Larus J Gudmundsson, Gyda Bjornsdottir, Kristleifur Kristjansson, Halla Skuladottir, Helgi J Isaksson, Tomas Gudbjartsson, Gregory T Jones, Thomas Mueller, Anders Gottsäter, Andrea Flex, Katja K H Aben, Femmie de Vegt, Peter F A Mulders, Dolores Isla, Maria J Vidal, Laura Asin, Berta Saez, Laura Murillo, Thorsteinn Blondal, Halldor Kolbeinsson, Jon G Stefansson, Ingunn Hansdottir, Valgerdur Runarsdottir, Roberto Pola, Bengt Lindblad, Andre M van Rij, Benjamin Dieplinger, Meinhard Haltmayer, Jose I Mayordomo, Lambertus A Kiemeney, Stefan E Matthiasson, Hogni Oskarsson, Thorarinn Tyrfingsson, Daniel F Gudbjartsson, Jeffrey R Gulcher, Steinn Jonsson, Unnur Thorsteinsdottir, Augustine Kong, Kari Stefansson, Thorgeir E Thorgeirsson, Frank Geller, Patrick Sulem, Thorunn Rafnar, Anna Wiste, Kristinn P Magnusson, Andrei Manolescu, Gudmar Thorleifsson, Hreinn Stefansson, Andres Ingason, Simon N Stacey, Jon T Bergthorsson, Steinunn Thorlacius, Julius Gudmundsson, Thorlakur Jonsson, Margret Jakobsdottir, Jona Saemundsdottir, Olof Olafsdottir, Larus J Gudmundsson, Gyda Bjornsdottir, Kristleifur Kristjansson, Halla Skuladottir, Helgi J Isaksson, Tomas Gudbjartsson, Gregory T Jones, Thomas Mueller, Anders Gottsäter, Andrea Flex, Katja K H Aben, Femmie de Vegt, Peter F A Mulders, Dolores Isla, Maria J Vidal, Laura Asin, Berta Saez, Laura Murillo, Thorsteinn Blondal, Halldor Kolbeinsson, Jon G Stefansson, Ingunn Hansdottir, Valgerdur Runarsdottir, Roberto Pola, Bengt Lindblad, Andre M van Rij, Benjamin Dieplinger, Meinhard Haltmayer, Jose I Mayordomo, Lambertus A Kiemeney, Stefan E Matthiasson, Hogni Oskarsson, Thorarinn Tyrfingsson, Daniel F Gudbjartsson, Jeffrey R Gulcher, Steinn Jonsson, Unnur Thorsteinsdottir, Augustine Kong, Kari Stefansson
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.
Source: PubMed