Sammanfattning
| Originalspråk | engelska |
|---|---|
| Tidskrift | Nature Genetics |
| Volym | 42 |
| Sidor (från-till) | 448-453 |
| Antal sidor | 6 |
| ISSN | 1061-4036 |
| DOI | |
| Status | Publicerad - 2010 |
| MoE-publikationstyp | A1 Tidskriftsartikel-refererad |
Vetenskapsgrenar
- 314 Hälsovetenskap
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Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. / Thorgeirsson, Thorgeir E.; Gudbjartsson, Daniel F.; Surakka, Ida Liisa; Vink, Jacqueline M.; Amin, Najaf; Geller, Frank; Sulem, Patrick; Rafnar, Thorunn; Esko, Tonu; Walter, Stefan; Gieger, Christian; Rawal, Rajesh; Mangino, Massimo; Prokopenko, Inga; Maegi, Reedik; Keskitalo, Kaisu; Gudjonsdottir, Iris H.; Gretarsdottir, Solveig; Stefansson, Hreinn; Thompson, John R.; Aulchenko, Yurii S.; Nelis, Mari; Aben, Katja K.; den Heijer, Martin; Dirksen, Asger; Ashraf, Haseem; Soranzo, Nicole; Valdes, Ana M.; Steves, Claire; Uitterlinden, Andre G.; Hofman, Albert; Toenjes, Anke; Kovacs, Peter; Hottenga, Jouke Jan; Willemsen, Gonneke; Vogelzangs, Nicole; Doering, Angela; Dahmen, Norbert; Nitz, Barbara; Pergadia, Michele L.; Saez, Berta; De Diego, Veronica; Lezcano, Victoria; Garcia-Prats, Maria D.; Ripatti, Samuli Olli; Perola, Markus; Kettunen, Johannes; Shen, Huei-Yi; Kaprio, Jaakko; Palotie, Leena; ENGAGE Consortium.
I: Nature Genetics, Vol. 42, 2010, s. 448-453.Forskningsoutput: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review
TY - JOUR
T1 - Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior
AU - Thorgeirsson, Thorgeir E.
AU - Gudbjartsson, Daniel F.
AU - Surakka, Ida Liisa
AU - Vink, Jacqueline M.
AU - Amin, Najaf
AU - Geller, Frank
AU - Sulem, Patrick
AU - Rafnar, Thorunn
AU - Esko, Tonu
AU - Walter, Stefan
AU - Gieger, Christian
AU - Rawal, Rajesh
AU - Mangino, Massimo
AU - Prokopenko, Inga
AU - Maegi, Reedik
AU - Keskitalo, Kaisu
AU - Gudjonsdottir, Iris H.
AU - Gretarsdottir, Solveig
AU - Stefansson, Hreinn
AU - Thompson, John R.
AU - Aulchenko, Yurii S.
AU - Nelis, Mari
AU - Aben, Katja K.
AU - den Heijer, Martin
AU - Dirksen, Asger
AU - Ashraf, Haseem
AU - Soranzo, Nicole
AU - Valdes, Ana M.
AU - Steves, Claire
AU - Uitterlinden, Andre G.
AU - Hofman, Albert
AU - Toenjes, Anke
AU - Kovacs, Peter
AU - Hottenga, Jouke Jan
AU - Willemsen, Gonneke
AU - Vogelzangs, Nicole
AU - Doering, Angela
AU - Dahmen, Norbert
AU - Nitz, Barbara
AU - Pergadia, Michele L.
AU - Saez, Berta
AU - De Diego, Veronica
AU - Lezcano, Victoria
AU - Garcia-Prats, Maria D.
AU - Ripatti, Samuli Olli
AU - Perola, Markus
AU - Kettunen, Johannes
AU - Shen, Huei-Yi
AU - Kaprio, Jaakko
AU - Palotie, Leena
AU - ENGAGE Consortium
PY - 2010
Y1 - 2010
N2 - Smoking is a common risk factor for many diseases. We conducted genome-wide association meta-analyses for the number of cigarettes smoked per day (CPD) in smokers (n = 31,266) and smoking initiation (n = 46,481) using samples from the ENGAGE Consortium. In a second stage, we tested selected SNPs with in silico replication in the Tobacco and Genetics (TAG) and Glaxo Smith Kline (Ox-GSK) consortia cohorts (n = 45,691 smokers) and assessed some of those in a third sample of European ancestry (n = 9,040). Variants in three genomic regions associated with CPD (P < 5 x 10(-8)), including previously identified SNPs at 15q25 represented by rs1051730[A] (effect size = 0.80 CPD, P = 2.4 x 10(-69)), and SNPs at 19q13 and 8p11, represented by rs4105144[C] (effect size = 0.39 CPD, P = 2.2 x 10(-12)) and rs6474412-T (effect size = 0.29 CPD, P = 1.4 x 10(-8)), respectively. Among the genes at the two newly associated loci are genes encoding nicotine-metabolizing enzymes (CYP2A6 and CYP2B6) and nicotinic acetylcholine receptor subunits (CHRNB3 and CHRNA6), all of which have been highlighted in previous studies of smoking and nicotine dependence. Nominal associations with lung cancer were observed at both 8p11 (rs6474412[T], odds ratio (OR) = 1.09, P = 0.04) and 19q13 (rs4105144[C], OR = 1.12, P = 0.0006).
AB - Smoking is a common risk factor for many diseases. We conducted genome-wide association meta-analyses for the number of cigarettes smoked per day (CPD) in smokers (n = 31,266) and smoking initiation (n = 46,481) using samples from the ENGAGE Consortium. In a second stage, we tested selected SNPs with in silico replication in the Tobacco and Genetics (TAG) and Glaxo Smith Kline (Ox-GSK) consortia cohorts (n = 45,691 smokers) and assessed some of those in a third sample of European ancestry (n = 9,040). Variants in three genomic regions associated with CPD (P < 5 x 10(-8)), including previously identified SNPs at 15q25 represented by rs1051730[A] (effect size = 0.80 CPD, P = 2.4 x 10(-69)), and SNPs at 19q13 and 8p11, represented by rs4105144[C] (effect size = 0.39 CPD, P = 2.2 x 10(-12)) and rs6474412-T (effect size = 0.29 CPD, P = 1.4 x 10(-8)), respectively. Among the genes at the two newly associated loci are genes encoding nicotine-metabolizing enzymes (CYP2A6 and CYP2B6) and nicotinic acetylcholine receptor subunits (CHRNB3 and CHRNA6), all of which have been highlighted in previous studies of smoking and nicotine dependence. Nominal associations with lung cancer were observed at both 8p11 (rs6474412[T], odds ratio (OR) = 1.09, P = 0.04) and 19q13 (rs4105144[C], OR = 1.12, P = 0.0006).
KW - GENOME-WIDE ASSOCIATION
KW - NICOTINIC ACETYLCHOLINE-RECEPTORS
KW - LUNG-CANCER
KW - SUSCEPTIBILITY LOCUS
KW - MOLECULAR-GENETICS
KW - HEAVY SMOKING
KW - ADULT TWINS
KW - DEPENDENCE
KW - GENES
KW - SNPS
KW - 314 Health sciences
U2 - 10.1038/ng.573
DO - 10.1038/ng.573
M3 - Article
VL - 42
SP - 448
EP - 453
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -