| Literature DB >> 18385739 |
Thorgeir E Thorgeirsson1, Frank Geller1, Patrick Sulem1, Thorunn Rafnar1, Anna Wiste1,2, Kristinn P Magnusson1, Andrei Manolescu1, Gudmar Thorleifsson1, Hreinn Stefansson1, Andres Ingason1, Simon N Stacey1, Jon T Bergthorsson1, Steinunn Thorlacius1, Julius Gudmundsson1, Thorlakur Jonsson1, Margret Jakobsdottir1, Jona Saemundsdottir1, Olof Olafsdottir1, Larus J Gudmundsson1, Gyda Bjornsdottir1, Kristleifur Kristjansson1, Halla Skuladottir3, Helgi J Isaksson4, Tomas Gudbjartsson5, Gregory T Jones6, Thomas Mueller7, Anders Gottsäter8, Andrea Flex9, Katja K H Aben10,11, Femmie de Vegt10, Peter F A Mulders12, Dolores Isla13, Maria J Vidal13, Laura Asin14, Berta Saez15, Laura Murillo16, Thorsteinn Blondal17, Halldor Kolbeinsson18, Jon G Stefansson18, Ingunn Hansdottir19, Valgerdur Runarsdottir19, Roberto Pola9, Bengt Lindblad8, Andre M van Rij6, Benjamin Dieplinger7, Meinhard Haltmayer7, Jose I Mayordomo13,14,15, Lambertus A Kiemeney10,11,12, Stefan E Matthiasson20, Hogni Oskarsson21, Thorarinn Tyrfingsson19, Daniel F Gudbjartsson1, Jeffrey R Gulcher1, Steinn Jonsson22, Unnur Thorsteinsdottir1,20, Augustine Kong1, Kari Stefansson1,20.
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.Entities:
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Year: 2008 PMID： 18385739 PMCID： PMC4539558 DOI： 10.1038/nature06846
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962