A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.
Thorgeir E. Thorgeirsson,Frank Geller,Patrick Sulem,Thorunn Rafnar,Anna Wiste,Anna Wiste,Kristinn P. Magnusson,Andrei Manolescu,Gudmar Thorleifsson,Hreinn Stefansson,Andres Ingason,Simon N. Stacey,Jon Thor Bergthorsson,Steinunn Thorlacius,Julius Gudmundsson,Thorlakur Jonsson,Margret Jakobsdottir,Jona Saemundsdottir,Olof Birna 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 Vidal,Laura Asín,Berta Saez,L. Murillo,Thorsteinn Blondal,Halldor Kolbeinsson,Jón G. Stefánsson,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,Unnur Thorsteinsdottir,Augustine Kong,Kari Stefansson,Kari Stefansson +59 more
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TLDR
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 is identified.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.read more
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Li Ding,Gad Getz,David A. Wheeler,Elaine R. Mardis,Michael D. McLellan,Kristian Cibulskis,Carrie Sougnez,Heidi Greulich,Heidi Greulich,Donna M. Muzny,Margaret Morgan,Lucinda Fulton,Robert S. Fulton,Qunyuan Zhang,Michael C. Wendl,Michael S. Lawrence,David E. Larson,Ken Chen,David J. Dooling,Aniko Sabo,Alicia Hawes,Hua Shen,Shalini N. Jhangiani,Lora Lewis,Otis Hall,Yiming Zhu,Tittu Mathew,Yanru Ren,Jiqiang Yao,Steven E. Scherer,Kerstin Clerc,Ginger A. Metcalf,Brian Ng,Aleksandar Milosavljevic,Manuel L. Gonzalez-Garay,John R. Osborne,Rick Meyer,Xiaoqi Shi,Yuzhu Tang,Daniel C. Koboldt,Ling Lin,Rachel Abbott,Tracie L. Miner,Craig Pohl,Ginger A. Fewell,Carrie A. Haipek,Heather Schmidt,Brian H. Dunford-Shore,Aldi T. Kraja,Seth D. Crosby,Christopher S. Sawyer,Tammi L. Vickery,Sacha N. Sander,Jody S. Robinson,Wendy Winckler,Wendy Winckler,Jennifer Baldwin,Lucian R. Chirieac,Amit Dutt,Amit Dutt,Timothy Fennell,Megan Hanna,Megan Hanna,Bruce E. Johnson,Robert C. Onofrio,Roman K. Thomas,Giovanni Tonon,Barbara A. Weir,Barbara A. Weir,Xiaojun Zhao,Xiaojun Zhao,Liuda Ziaugra,Michael C. Zody,Thomas J. Giordano,Mark B. Orringer,Jack A. Roth,Margaret R. Spitz,Ignacio I. Wistuba,Bradley A. Ozenberger,Peter J. Good,Andrew C. Chang,David G. Beer,Mark A. Watson,Marc Ladanyi,Stephen R. Broderick,Akihiko Yoshizawa,William D. Travis,William Pao,Michael A. Province,George M. Weinstock,Harold E. Varmus,Stacey Gabriel,Eric S. Lander,Richard A. Gibbs,Matthew Meyerson,Matthew Meyerson,Richard K. Wilson +96 more
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Genome-wide meta-analyses identify multiple loci associated with smoking behavior
Helena Furberg,Yunjung Kim,Jennifer Dackor,Eric Boerwinkle,Nora Franceschini,Diego Ardissino,Luisa Bernardinelli,Luisa Bernardinelli,Pier Mannuccio Mannucci,Francesco Mauri,Piera Angelica Merlini,Devin Absher,Themistocles L. Assimes,Stephen P. Fortmann,Carlos Iribarren,Joshua W. Knowles,Thomas Quertermous,Luigi Ferrucci,Toshiko Tanaka,Joshua C. Bis,Curt D. Furberg,Talin Haritunians,Barbara McKnight,Bruce M. Psaty,Bruce M. Psaty,Kent D. Taylor,Evan L. Thacker,Peter Almgren,Leif Groop,Claes Ladenvall,Michael Boehnke,Anne U. Jackson,Karen L. Mohlke,Heather M. Stringham,Jaakko Tuomilehto,Jaakko Tuomilehto,Emelia J. Benjamin,Shih-Jen Hwang,Daniel Levy,Sarah R. Preis,Ramachandran S. Vasan,Jubao Duan,Pablo V. Gejman,Douglas F. Levinson,Alan R. Sanders,Jianxin Shi,Esther H. Lips,James McKay,Antonio Agudo,Luigi Barzan,Vladimir Bencko,Simone Benhamou,Simone Benhamou,Xavier Castellsagué,Cristina Canova,David I. Conway,Eleonora Fabianova,Lenka Foretova,Vladimir Janout,Claire M. Healy,Ivana Holcatova,Kristina Kjærheim,Pagona Lagiou,Jolanta Lissowska,Ray Lowry,Tatiana V. Macfarlane,Dana Mates,Lorenzo Richiardi,Peter Rudnai,Neonilia Szeszenia-Dabrowska,David Zaridze,Ariana Znaor,Mark Lathrop,Paul Brennan,Stefania Bandinelli,Timothy M. Frayling,Jack M. Guralnik,Yuri Milaneschi,John R. B. Perry,David Altshuler,David Altshuler,Roberto Elosua,S. Kathiresan,S. Kathiresan,Gavin Lucas,Olle Melander,Christopher J. O'Donnell,Veikko Salomaa,Stephen M. Schwartz,Benjamin F. Voight,Brenda W.J.H. Penninx,Johannes H. Smit,Nicole Vogelzangs,Dorret I. Boomsma,Eco J. C. de Geus,Jacqueline M. Vink,Gonneke Willemsen,Stephen J. Chanock,Fangyi Gu,Susan E. Hankinson,David J. Hunter,Albert Hofman,Henning Tiemeier,André G. Uitterlinden,Cornelia M. van Duijn,Stefan Walter,Daniel I. Chasman,Brendan M. Everett,Guillaume Paré,Paul M. Ridker,Ming D. Li,Hermine H. Maes,Janet Audrain-McGovern,Danielle Posthuma,Laura M. Thornton,Caryn Lerman,Jaakko Kaprio,Jaakko Kaprio,Jed E. Rose,John P. A. Ioannidis,John P. A. Ioannidis,Peter Kraft,Danyu Lin,Patrick F. Sullivan +123 more
TL;DR: A meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium found the strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3, and three loci associated with number of cigarettes smoked per day were identified.
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