|
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| PMID |
|
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| TITLE |
|
| Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. |
|
| ABSTRACT |
|
|
|
| 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). |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| received |
2009/10/21 |
| accepted |
2010/03/18 |
| aheadofprint |
2010/04/25 |
| entrez |
2010/04/27 06:00 |
| pubmed |
2010/04/27 06:00 |
| medline |
2010/05/28 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Thorgeirsson TE |
|
Thorgeirsson |
Thorgeir E |
TE |
|
[1] deCODE Genetics, Reykjavik, Iceland. [2] Center for Biomolecular Science and Engineering, Jack Baskin School of Engineering, University of California, Santa Cruz, California, USA. |
| Gudbjartsson DF |
|
Gudbjartsson |
Daniel F |
DF |
|
|
| Surakka I |
|
Surakka |
Ida |
I |
|
|
| Vink JM |
|
Vink |
Jacqueline M |
JM |
|
|
| Amin N |
|
Amin |
Najaf |
N |
|
|
| Geller F |
|
Geller |
Frank |
F |
|
|
| Sulem P |
|
Sulem |
Patrick |
P |
|
|
| Rafnar T |
|
Rafnar |
Thorunn |
T |
|
|
| Esko T |
|
Esko |
Tõnu |
T |
|
|
| Walter S |
|
Walter |
Stefan |
S |
|
|
| Gieger C |
|
Gieger |
Christian |
C |
|
|
| Rawal R |
|
Rawal |
Rajesh |
R |
|
|
| Mangino M |
|
Mangino |
Massimo |
M |
|
|
| Prokopenko I |
|
Prokopenko |
Inga |
I |
|
|
| Mägi R |
|
Mägi |
Reedik |
R |
|
|
| Keskitalo K |
|
Keskitalo |
Kaisu |
K |
|
|
| Gudjonsdottir IH |
|
Gudjonsdottir |
Iris H |
IH |
|
|
| Gretarsdottir S |
|
Gretarsdottir |
Solveig |
S |
|
|
| Stefansson H |
|
Stefansson |
Hreinn |
H |
|
|
| Thompson JR |
|
Thompson |
John R |
JR |
|
|
| Aulchenko YS |
|
Aulchenko |
Yurii S |
YS |
|
|
| Nelis M |
|
Nelis |
Mari |
M |
|
|
| Aben KK |
|
Aben |
Katja K |
KK |
|
|
| den Heijer M |
|
den Heijer |
Martin |
M |
|
|
| Dirksen A |
|
Dirksen |
Asger |
A |
|
|
| Ashraf H |
|
Ashraf |
Haseem |
H |
|
|
| Soranzo N |
|
Soranzo |
Nicole |
N |
|
|
| Valdes AM |
|
Valdes |
Ana M |
AM |
|
|
| Steves C |
|
Steves |
Claire |
C |
|
|
| Uitterlinden AG |
|
Uitterlinden |
André G |
AG |
|
|
| Hofman A |
|
Hofman |
Albert |
A |
|
|
| Tönjes A |
|
Tönjes |
Anke |
A |
|
|
| Kovacs P |
|
Kovacs |
Peter |
P |
|
|
| Hottenga JJ |
|
Hottenga |
Jouke Jan |
JJ |
|
|
| Willemsen G |
|
Willemsen |
Gonneke |
G |
|
|
| Vogelzangs N |
|
Vogelzangs |
Nicole |
N |
|
|
| Döring A |
|
Döring |
Angela |
A |
|
|
| Dahmen N |
|
Dahmen |
Norbert |
N |
|
|
| Nitz B |
|
Nitz |
Barbara |
B |
|
|
| Pergadia ML |
|
Pergadia |
Michele L |
ML |
|
|
| Saez B |
|
Saez |
Berta |
B |
|
|
| De Diego V |
|
De Diego |
Veronica |
V |
|
|
| Lezcano V |
|
Lezcano |
Victoria |
V |
|
|
| Garcia-Prats MD |
|
Garcia-Prats |
Maria D |
MD |
|
|
| Ripatti S |
|
Ripatti |
Samuli |
S |
|
|
| Perola M |
|
Perola |
Markus |
M |
|
|
| Kettunen J |
|
Kettunen |
Johannes |
J |
|
|
| Hartikainen AL |
|
Hartikainen |
Anna-Liisa |
AL |
|
|
| Pouta A |
|
Pouta |
Anneli |
A |
|
|
| Laitinen J |
|
Laitinen |
Jaana |
J |
|
|
| Isohanni M |
|
Isohanni |
Matti |
M |
|
|
| Huei-Yi S |
|
Huei-Yi |
Shen |
S |
|
|
| Allen M |
|
Allen |
Maxine |
M |
|
|
| Krestyaninova M |
|
Krestyaninova |
Maria |
M |
|
|
| Hall AS |
|
Hall |
Alistair S |
AS |
|
|
| Jones GT |
|
Jones |
Gregory T |
GT |
|
|
| van Rij AM |
|
van Rij |
Andre M |
AM |
|
|
| Mueller T |
|
Mueller |
Thomas |
T |
|
|
| Dieplinger B |
|
Dieplinger |
Benjamin |
B |
|
|
| Haltmayer M |
|
Haltmayer |
Meinhard |
M |
|
|
| Jonsson S |
|
Jonsson |
Steinn |
S |
|
|
| Matthiasson SE |
|
Matthiasson |
Stefan E |
SE |
|
|
| Oskarsson H |
|
Oskarsson |
Hogni |
H |
|
|
| Tyrfingsson T |
|
Tyrfingsson |
Thorarinn |
T |
|
|
| Kiemeney LA |
|
Kiemeney |
Lambertus A |
LA |
|
|
| Mayordomo JI |
|
Mayordomo |
Jose I |
JI |
|
|
| Lindholt JS |
|
Lindholt |
Jes S |
JS |
|
|
| Pedersen JH |
|
Pedersen |
Jesper Holst |
JH |
|
|
| Franklin WA |
|
Franklin |
Wilbur A |
WA |
|
|
| Wolf H |
|
Wolf |
Holly |
H |
|
|
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
|
| Heath AC |
|
Heath |
Andrew C |
AC |
|
|
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
|
| Madden PA |
|
Madden |
Pamela A F |
PA |
|
|
| Giegling I |
|
Giegling |
Ina |
I |
|
|
| Rujescu D |
|
Rujescu |
Dan |
D |
|
|
| Järvelin MR |
|
Järvelin |
Marjo-Riitta |
MR |
|
|
| Salomaa V |
|
Salomaa |
Veikko |
V |
|
|
| Stumvoll M |
|
Stumvoll |
Michael |
M |
|
|
| Spector TD |
|
Spector |
Tim D |
TD |
|
|
| Wichmann HE |
|
Wichmann |
H-Erich |
HE |
|
|
| Metspalu A |
|
Metspalu |
Andres |
A |
|
|
| Samani NJ |
|
Samani |
Nilesh J |
NJ |
|
|
| Penninx BW |
|
Penninx |
Brenda W |
BW |
|
|
| Oostra BA |
|
Oostra |
Ben A |
BA |
|
|
| Boomsma DI |
|
Boomsma |
Dorret I |
DI |
|
|
| Tiemeier H |
|
Tiemeier |
Henning |
H |
|
|
| van Duijn CM |
|
van Duijn |
Cornelia M |
CM |
|
|
| Kaprio J |
|
Kaprio |
Jaakko |
J |
|
|
| Gulcher JR |
|
Gulcher |
Jeffrey R |
JR |
|
|
|
ENGAGE Consortium |
|
|
|
|
|
| McCarthy MI |
|
McCarthy |
Mark I |
MI |
|
|
| Peltonen L |
|
Peltonen |
Leena |
L |
|
|
| Thorsteinsdottir U |
|
Thorsteinsdottir |
Unnur |
U |
|
|
| Stefansson K |
|
Stefansson |
Kari |
K |
|
|
|
| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Peltonen |
Leena |
L |
|
| Kaprio |
Jaakko |
J |
|
| Ripatti |
Samuli |
S |
|
| Perola |
Markus |
M |
|
| McCarthy |
Mark |
M |
|
| Brasma |
Alvis |
A |
|
| Evans |
Alun |
A |
|
| Spector |
Tim |
T |
|
| Bentley |
David |
D |
|
| Ross |
Mark |
M |
|
| van Ommen |
Gert-Jan |
GJ |
|
| Boomsma |
Dorret |
D |
|
| Pennix |
Brenda |
B |
|
| Hofman |
Albert |
A |
|
| van Duijn |
Cornelia |
C |
|
| Wichman |
Erich |
E |
|
| Illig |
Thomas |
T |
|
| Geiger |
Christian |
C |
|
| Pedersen |
Nancy |
N |
|
| Groop |
Leif |
L |
|
| Uhlen |
Mathias |
M |
|
| Harris |
Jennifer |
J |
|
| Metspalu |
Andres |
A |
|
| Stefansson |
Kari |
K |
|
| Thorsteinsdottir |
Unnur |
U |
|
| Hudson |
Thomas |
T |
|
| Knoppers |
Bartha Maria |
BM |
|
| Estivill |
Xavier |
X |
|
| Samani |
Nilesh |
N |
|
| Jarvelin |
Marjo-Riitta |
MR |
|
| Martin |
Nick |
N |
|
| Whitfield |
John |
J |
|
| Peltonen |
Leena |
L |
|
| Palotie |
Aarno |
A |
|
| Viskna |
Juris |
J |
|
|
| JOURNAL |
|
| VOLUME: 42 |
| ISSUE: 5 |
| TITLE: Nature genetics |
| ISOABBREVIATION: Nat. Genet. |
| YEAR: 2010 |
| MONTH: May |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1546-1718 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Nat Genet |
| COUNTRY: United States |
| ISSNLINKING: 1061-4036 |
| NLMUNIQUEID: 9216904 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| Cites |
J Neurogenet. 2009;23(3):252-61 |
19169923 |
|
| Cites |
PLoS Genet. 2009 Mar;5(3):e1000421 |
19300482 |
|
| Cites |
Hum Mol Genet. 2009 Oct 15;18(20):4007-12 |
19628476 |
|
| Cites |
Bioinformatics. 2009 Oct 15;25(20):2768-9 |
19633095 |
|
| Cites |
Int J Epidemiol. 2010 Apr;39(2):563-77 |
19776245 |
|
| Cites |
Int J Epidemiol. 2010 Apr;39(2):577-9 |
20123949 |
|
| Cites |
Annu Rev Genomics Hum Genet. 2009;10:387-406 |
19715440 |
|
| Cites |
Behav Genet. 1999 Nov;29(6):383-93 |
10857244 |
|
| Cites |
Biometrics. 1999 Dec;55(4):997-1004 |
11315092 |
|
| Cites |
Stat Med. 2002 Jun 15;21(11):1539-58 |
12111919 |
|
| Cites |
Addiction. 2003 Jan;98(1):23-31 |
12492752 |
|
| Cites |
J Clin Invest. 2003 Jan;111(1):81-90 |
12511591 |
|
| Cites |
Neuropharmacology. 2003 Jul;45(1):122-32 |
12814665 |
|
| Cites |
Nature. 2005 Oct 27;437(7063):1299-320 |
16255080 |
|
| Cites |
Nucleic Acids Res. 2006;34(19):e128 |
17012270 |
|
| Cites |
Hum Mol Genet. 2007 Jan 1;16(1):36-49 |
17135278 |
|
| Cites |
Hum Mol Genet. 2007 Jan 1;16(1):24-35 |
17158188 |
|
| Cites |
BMC Genet. 2007;8:10 |
17407593 |
|
| Cites |
Nat Genet. 2007 Jul;39(7):906-13 |
17572673 |
|
| Cites |
Biochem Pharmacol. 2008 Jan 1;75(1):323-33 |
17632086 |
|
| Cites |
Mol Psychiatry. 2008 Apr;13(4):368-73 |
18227835 |
|
| Cites |
Nature. 2008 Apr 3;452(7187):537-8 |
18385720 |
|
| Cites |
Nature. 2008 Apr 3;452(7187):633-7 |
18385738 |
|
| Cites |
Nature. 2008 Apr 3;452(7187):638-42 |
18385739 |
|
| Cites |
Nat Genet. 2008 May;40(5):616-22 |
18385676 |
|
| Cites |
Arch Gen Psychiatry. 2008 Jun;65(6):683-93 |
18519826 |
|
| Cites |
J Natl Cancer Inst. 2008 Nov 5;100(21):1552-6 |
18957677 |
|
| Cites |
Biol Psychiatry. 2008 Dec 1;64(11):919-21 |
19000575 |
|
| Cites |
Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3517-25 |
19029397 |
|
| Cites |
Handb Exp Pharmacol. 2009;(192):85-112 |
19184647 |
|
| CommentIn |
Nat Genet. 2010 May;42(5):366-8 |
20428092 |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| 072856 |
Wellcome Trust |
United Kingdom |
| 079771 |
Wellcome Trust |
United Kingdom |
| 089061 |
Wellcome Trust |
United Kingdom |
| R01 DA 017932 |
NIDA NIH HHS |
United States |
| R01 DA017932 |
NIDA NIH HHS |
United States |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Alleles |
|
| Aryl Hydrocarbon Hydroxylases |
genetics |
| Cohort Studies |
genetics |
| Cytochrome P-450 CYP2A6 |
genetics |
| Female |
genetics |
| Genetic Variation |
genetics |
| Genome-Wide Association Study |
genetics |
| Genomics |
genetics |
| Humans |
genetics |
| Lung Neoplasms |
genetics |
| Male |
genetics |
| Odds Ratio |
genetics |
| Phenotype |
genetics |
| Receptors, Nicotinic |
genetics |
| Smoking |
genetics |
| Tobacco Use Disorder |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
CHRNA6 protein, human |
| 0 |
CHRNB3 protein, human |
| 0 |
CYP2A6 protein, human |
| 0 |
Receptors, Nicotinic |
| EC 1.14.13.- |
Cytochrome P-450 CYP2A6 |
| EC 1.14.14.1 |
Aryl Hydrocarbon Hydroxylases |
|
| OTHER ID's |
|
| OTHERID |
SOURCE |
| PMC3080600 |
NLM |
| UKMS35137 |
NLM |
|
|
