Περίληψη:
Consistent but indirect evidence has implicated genetic factors in
smoking behavior1,2. We report meta-analyses of several smoking
phenotypes within cohorts of the Tobacco and Genetics Consortium (n =
74,053). We also partnered with the European Network of Genetic and
Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK)
consortia to follow up the 15 most significant regions (n > 140,000). We
identified three loci associated with number of cigarettes smoked per
day. The strongest association was a synonymous 15q25 SNP in the
nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error
(s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b
= 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b =
0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2
(rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also
exceeded genome-wide significance for cigarettes per day. For smoking
initiation, eight SNPs exceeded genome-wide significance, with the
strongest association at a nonsynonymous SNP in BDNF on chromosome 11
(rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl)
1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9
(rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was
significantly associated with smoking cessation.
Συγγραφείς:
Furberg, Helena
Kim, YunJung
Dackor, Jennifer
Boerwinkle,
Eric
Franceschini, Nora
Ardissino, Diego
Bernardinelli,
Luisa
Mannucci, Pier M.
Mauri, Francesco
Merlini, Piera A.
and Absher, Devin
Assimes, Themistocles L.
Fortmann, Stephen P.
and Iribarren, Carlos
Knowles, Joshua W.
Quertermous, Thomas and
Ferrucci, Luigi
Tanaka, Toshiko
Bis, Joshua C.
Furberg, Curt
D.
Haritunians, Talin
McKnight, Barbara
Psaty, Bruce M. and
Taylor, Kent D.
Thacker, Evan L.
Almgren, Peter
Groop, Leif
and Ladenvall, Claes
Boehnke, Michael
Jackson, Anne U. and
Mohlke, Karen L.
Stringham, Heather M.
Tuomilehto, Jaakko and
Benjamin, Emelia J.
Hwang, Shih-Jen
Levy, Daniel
Preis,
Sarah Rosner
Vasan, Ramachandran S.
Duan, Jubao
Gejman,
Pablo V.
Levinson, Douglas F.
Sanders, Alan R.
Shi, Jianxin
and Lips, Esther H.
Mckay, James D.
Agudo, Antonio
Barzan,
Luigi
Bencko, Vladimir
Benhamou, Simone
Castellsague, Xavier
and Canova, Cristina
Conway, David I.
Fabianova, Eleonora and
Foretova, Lenka
Janout, Vladimir
Healy, Claire M.
Holcatova,
Ivana
Kjaerheim, Kristina
Lagiou, Pagona
Lissowska, Jolanta
and Lowry, Ray
Macfarlane, Tatiana V.
Mates, Dana
Richiardi,
Lorenzo
Rudnai, Peter
Szeszenia-Dabrowska, Neonilia
Zaridze,
David
Znaor, Ariana
Lathrop, Mark
Brennan, Paul and
Bandinelli, Stefania
Frayling, Timothy M.
Guralnik, Jack M. and
Milaneschi, Yuri
Perry, John R. B.
Altshuler, David
Elosua,
Roberto
Kathiresan, Sek
Lucas, Gavin
Melander, Olle and
O'Donnell, Christopher J.
Salomaa, Veikko
Schwartz, Stephen M.
and Voight, Benjamin F.
Penninx, Brenda W.
Smit, Johannes H. and
Vogelzangs, Nicole
Boomsma, Dorret I.
de Geus, Eco J. C. and
Vink, Jacqueline M.
Willemsen, Gonneke
Chanock, Stephen J. and
Gu, Fangyi
Hankinson, Susan E.
Hunter, David J.
Hofman,
Albert
Tiemeier, Henning
Uitterlinden, Andre G.
van Duijn,
Cornelia M.
Walter, Stefan
Chasman, Daniel I.
Everett,
Brendan M.
Pare, Guillaume
Ridker, Paul M.
Li, Ming D. and
Maes, Hermine H.
Audrain-McGovern, Janet
Posthuma, Danielle and
Thornton, Laura M.
Lerman, Caryn
Kaprio, Jaakko
Rose, Jed E.
and Ioannidis, John P. A.
Kraft, Peter
Lin, Dan-Yu
Sullivan,
Patrick F.
