Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
24186853
TITLE
Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.
ABSTRACT
Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype.
2013 WILEY PERIODICALS, INC.
DATE PUBLISHED
2013 Dec
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2013/01/11
revised 2013/06/21
accepted 2013/08/14
aheadofprint 2013/11/01
entrez 2013/11/05 06:00
pubmed 2013/11/05 06:00
medline 2014/05/13 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Stephens SH Stephens Sarah H SH Department of Epidemiology and Public Health, University of Maryland, Baltimore, Maryland, United States of America.
Hartz SM Hartz Sarah M SM
Hoft NR Hoft Nicole R NR
Saccone NL Saccone Nancy L NL
Corley RC Corley Robin C RC
Hewitt JK Hewitt John K JK
Hopfer CJ Hopfer Christian J CJ
Breslau N Breslau Naomi N
Coon H Coon Hilary H
Chen X Chen Xiangning X
Ducci F Ducci Francesca F
Dueker N Dueker Nicole N
Franceschini N Franceschini Nora N
Frank J Frank Josef J
Han Y Han Younghun Y
Hansel NN Hansel Nadia N NN
Jiang C Jiang Chenhui C
Korhonen T Korhonen Tellervo T
Lind PA Lind Penelope A PA
Liu J Liu Jason J
Lyytikäinen LP Lyytikäinen Leo-Pekka LP
Michel M Michel Martha M
Shaffer JR Shaffer John R JR
Short SE Short Susan E SE
Sun J Sun Juzhong J
Teumer A Teumer Alexander A
Thompson JR Thompson John R JR
Vogelzangs N Vogelzangs Nicole N
Vink JM Vink Jacqueline M JM
Wenzlaff A Wenzlaff Angela A
Wheeler W Wheeler William W
Yang BZ Yang Bao-Zhu BZ
Aggen SH Aggen Steven H SH
Balmforth AJ Balmforth Anthony J AJ
Baumeister SE Baumeister Sebastian E SE
Beaty TH Beaty Terri H TH
Benjamin DJ Benjamin Daniel J DJ
Bergen AW Bergen Andrew W AW
Broms U Broms Ulla U
Cesarini D Cesarini David D
Chatterjee N Chatterjee Nilanjan N
Chen J Chen Jingchun J
Cheng YC Cheng Yu-Ching YC
Cichon S Cichon Sven S
Couper D Couper David D
Cucca F Cucca Francesco F
Dick D Dick Danielle D
Foroud T Foroud Tatiana T
Furberg H Furberg Helena H
Giegling I Giegling Ina I
Gillespie NA Gillespie Nathan A NA
Gu F Gu Fangyi F
Hall AS Hall Alistair S AS
Hällfors J Hällfors Jenni J
Han S Han Shizhong S
Hartmann AM Hartmann Annette M AM
Heikkilä K Heikkilä Kauko K
Hickie IB Hickie Ian B IB
Hottenga JJ Hottenga Jouke Jan JJ
Jousilahti P Jousilahti Pekka P
Kaakinen M Kaakinen Marika M
Kähönen M Kähönen Mika M
Koellinger PD Koellinger Philipp D PD
Kittner S Kittner Stephen S
Konte B Konte Bettina B
Landi MT Landi Maria-Teresa MT
Laatikainen T Laatikainen Tiina T
Leppert M Leppert Mark M
Levy SM Levy Steven M SM
Mathias RA Mathias Rasika A RA
McNeil DW McNeil Daniel W DW
Medland SE Medland Sarah E SE
Montgomery GW Montgomery Grant W GW
Murray T Murray Tanda T
Nauck M Nauck Matthias M
North KE North Kari E KE
Paré PD Paré Peter D PD
Pergadia M Pergadia Michele M
Ruczinski I Ruczinski Ingo I
Salomaa V Salomaa Veikko V
Viikari J Viikari Jorma J
Willemsen G Willemsen Gonneke G
Barnes KC Barnes Kathleen C KC
Boerwinkle E Boerwinkle Eric E
Boomsma DI Boomsma Dorret I DI
Caporaso N Caporaso Neil N
Edenberg HJ Edenberg Howard J HJ
Francks C Francks Clyde C
Gelernter J Gelernter Joel J
Grabe HJ Grabe Hans Jörgen HJ
Hops H Hops Hyman H
Jarvelin MR Jarvelin Marjo-Riitta MR
Johannesson M Johannesson Magnus M
Kendler KS Kendler Kenneth S KS
Lehtimäki T Lehtimäki Terho T
Magnusson PK Magnusson Patrik K E PK
Marazita ML Marazita Mary L ML
Marchini J Marchini Jonathan J
Mitchell BD Mitchell Braxton D BD
Nöthen MM Nöthen Markus M MM
Penninx BW Penninx Brenda W BW
Raitakari O Raitakari Olli O
Rietschel M Rietschel Marcella M
Rujescu D Rujescu Dan D
Samani NJ Samani Nilesh J NJ
Schwartz AG Schwartz Ann G AG
Shete S Shete Sanjay S
Spitz M Spitz Margaret M
Swan GE Swan Gary E GE
Völzke H Völzke Henry H
Veijola J Veijola Juha J
Wei Q Wei Qingyi Q
Amos C Amos Chris C
Cannon DS Cannon Dale S DS
Grucza R Grucza Richard R
Hatsukami D Hatsukami Dorothy D
Heath A Heath Andrew A
Johnson EO Johnson Eric O EO
Kaprio J Kaprio Jaakko J
Madden P Madden Pamela P
Martin NG Martin Nicholas G NG
Stevens VL Stevens Victoria L VL
Weiss RB Weiss Robert B RB
Kraft P Kraft Peter P
Bierut LJ Bierut Laura J LJ
Ehringer MA Ehringer Marissa A MA
INVESTIGATORS
JOURNAL
VOLUME: 37
ISSUE: 8
TITLE: Genetic epidemiology
ISOABBREVIATION: Genet. Epidemiol.
YEAR: 2013
MONTH: Dec
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1098-2272
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Genet Epidemiol
COUNTRY: United States
ISSNLINKING: 0741-0395
NLMUNIQUEID: 8411723
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Sci Am. 2008 May;298(5):82-7 18444329
Cites Biol Psychiatry. 2008 Jun 1;63(11):1039-46 18163978
Cites Int J Methods Psychiatr Res. 2008 Jun;17 Suppl 1:S30-8 18543360
Cites PLoS Genet. 2008 Jul;4(7):e1000125 18618000
Cites Am J Psychiatry. 2008 Sep;165(9):1163-71 18519524
Cites Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3517-25 19029397
Cites J Adolesc Health. 2009 Feb;44(2):103-10 19167657
Cites Prev Med. 1999 Nov;29(5):327-33 10564623
Cites Prev Med. 1999 Dec;29(6 Pt 1):590-8 10600442
Cites Am J Hum Genet. 2000 Jan;66(1):279-92 10631157
Cites Addiction. 1999 Jul;94(7):981-93 10707437
Cites Drug Alcohol Depend. 2000 May 1;59 Suppl 1:S61-81 10773438
Cites Am J Public Health. 2000 Aug;90(8):1307-11 10937016
Cites Tob Control. 2000 Sep;9(3):313-9 10982576
Cites Am J Med Genet. 2000 Oct 9;96(5):684-95 11054778
Cites Cancer Res. 2001 Jan 15;61(2):612-5 11212258
Cites Alcohol Clin Exp Res. 2001 Aug;25(8):1156-65 11505047
Cites Nicotine Tob Res. 2002 May;4(2):201-9 12028853
Cites Environ Health Perspect. 2002 Jun;110(6):555-8 12055044
Cites J Abnorm Psychol. 2002 Aug;111(3):411-24 12150417
Cites Tob Control. 2002 Sep;11(3):228-35 12198274
Cites Tob Control. 2002 Dec;11(4):354-60 12432161
Cites J Consult Clin Psychol. 2002 Dec;70(6):1224-39 12472299
Cites Addiction. 2003 Jan;98(1):23-31 12492752
Cites Am J Psychiatry. 2003 Jun;160(6):1078-85 12777265
Cites Psychol Addict Behav. 2003 Jun;17(2):151-8 12814279
Cites Arch Gen Psychiatry. 2003 Dec;60(12):1256-64 14662558
Cites JAMA. 1993 Mar 17;269(11):1391-5 8441214
Cites Drug Alcohol Depend. 1993 Sep;33(2):129-37 8261877
Cites Ann Epidemiol. 1994 Nov;4(6):455-9 7804500
Cites Am J Med Genet B Neuropsychiatr Genet. 2009 Jun 5;150B(4):453-66 19259974
Cites Addict Behav. 2009 Sep;34(9):772-5 19482438
Cites Cancer Res. 2009 Sep 1;69(17):6848-56 19706762
Cites Hum Mol Genet. 2009 Oct 15;18(20):4007-12 19628476
Cites Mol Psychiatry. 2009 Oct;14(10):912-45 19564872
Cites Nat Genet. 2010 May;42(5):448-53 20418888
Cites Nat Genet. 2010 May;42(5):436-40 20418889
Cites Pediatrics. 2010 Jun;125(6):1127-33 20439592
Cites J Natl Cancer Inst. 2010 Aug 4;102(15):1199-205 20554942
Cites PLoS Genet. 2010 Aug;6(8). pii: e1001053. doi: 10.1371/journal.pgen.1001053 20700436
Cites Nature. 2010 Sep 2;467(7311):52-8 20811451
Cites PLoS One. 2010;5(8):e12183 20808433
Cites Genes Brain Behav. 2010 Oct;9(7):741-50 20584212
Cites Am J Med Genet B Neuropsychiatr Genet. 2010 Dec 5;153B(8):1448-58 20886544
Cites Mol Pharmacol. 2011 Jan;79(1):119-25 20881005
Cites Biol Psychiatry. 2011 Apr 1;69(7):650-60 21168125
Cites Nature. 2011 Mar 31;471(7340):597-601 21278726
Cites Tob Control. 2011 May;20(3):201-6 21109683
Cites Br J Cancer. 2011 Apr 26;104(9):1500-4 21487403
Cites Neuropsychopharmacology. 2011 Jun;36(7):1412-20 21430647
Cites Genes Brain Behav. 2011 Jul;10(5):530-5 21418140
Cites Behav Genet. 2012 May;42(3):402-14 22042234
Cites Nicotine Tob Res. 2012 Jun;14(6):720-33 22241830
Cites Arch Gen Psychiatry. 2012 Aug;69(8):854-60 22868939
Cites Nature. 2012 Nov 1;491(7422):56-65 23128226
Cites Cold Spring Harb Perspect Med. 2013 Jan;3(1):a012112 23143843
Cites Psychol Med. 2011 Dec;41(12):2615-23 21733216
Cites Am J Public Health. 1996 Feb;86(2):214-20 8633738
Cites Health Rep. 1998 Spring;9(4):39-46(Eng); 39-48(Fre) 9836879
Cites Am J Hum Genet. 1999 Jan;64(1):259-67 9915965
Cites Prev Med. 1999 Apr;28(4):361-6 10090865
Cites J Natl Cancer Inst. 1999 Apr 7;91(7):614-9 10203280
Cites Bioinformatics. 2005 Jan 15;21(2):263-5 15297300
Cites MMWR Morb Mortal Wkly Rep. 2005 Jul 1;54(25):625-8 15988406
Cites Am J Health Behav. 2006 May-Jun;30(3):247-58 16712439
Cites Hum Mol Genet. 2007 Jan 1;16(1):36-49 17135278
Cites Am J Hum Genet. 2007 Sep;81(3):559-75 17701901
Cites Biochem Pharmacol. 2007 Oct 15;74(8):1263-70 17826746
Cites Pediatrics. 2007 Oct;120(4):e974-83 17908753
Cites Curr Psychiatry Rep. 2007 Oct;9(5):349-57 17915073
Cites Addict Behav. 2008 May;33(5):689-98 18207651
Cites Mol Psychiatry. 2008 Apr;13(4):368-73 18227835
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
GRANTS
GRANTID AGENCY COUNTRY
090532 Wellcome Trust United Kingdom
K01 DA19498 NIDA NIH HHS United States
K01 DA24758 NIDA NIH HHS United States
K02 AA018755 NIAAA NIH HHS United States
K02 AA018755 NIAAA NIH HHS United States
K02 DA021237 NIDA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
K07 CA118412 NCI NIH HHS United States
K08 DA032680 NIDA NIH HHS United States
K08 DA032680 NIDA NIH HHS United States
K99R00 DA023549 NIDA NIH HHS United States
KL2 RR024994 NCRR NIH HHS United States
KL2 RR024994 NCRR NIH HHS United States
KL2 TR000450 NCATS NIH HHS United States
N01-AG-1-2109 NIA NIH HHS United States
N01-PC35146 NCI NIH HHS United States
P01 AG005842 NIA NIH HHS United States
P01 CA089392 NCI NIH HHS United States
P01 CA089392 NCI NIH HHS United States
P30 CA016672 NCI NIH HHS United States
P30 DK-072488 NIDDK NIH HHS United States
P60 DA011015 NIDA NIH HHS United States
R01 AA017535 NIAAA NIH HHS United States
R01 AA07535 NIAAA NIH HHS United States
R01 AA07728 NIAAA NIH HHS United States
R01 AA11330 NIAAA NIH HHS United States
R01 AA11998 NIAAA NIH HHS United States
R01 AA13320 NIAAA NIH HHS United States
R01 AA14041 NIAAA NIH HHS United States
R01 AA17688 NIAAA NIH HHS United States
R01 CA060691 NCI NIH HHS United States
R01 CA87895 NCI NIH HHS United States
R01 DA012690 NIDA NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
R01 DA021913 NIDA NIH HHS United States
R01 DA026911 NIDA NIH HHS United States
R01 DA03706 NIDA NIH HHS United States
R01 DA12690 NIDA NIH HHS United States
R01 DA12849 NIDA NIH HHS United States
R01 DA12854 NIDA NIH HHS United States
R01 DE012101 NIDCR NIH HHS United States
R01 DE12101 NIDCR NIH HHS United States
R01 NS45012 NINDS NIH HHS United States
R01AA13321 NIAAA NIH HHS United States
R01HL089651-01 NHLBI NIH HHS United States
R21 DA027070 NIDA NIH HHS United States
R21 DA027070 NIDA NIH HHS United States
R24 HD041020 NICHD NIH HHS United States
T32 AG000186 NIA NIH HHS United States
U01 DA020830 NIDA NIH HHS United States
U01 DA02830 NIDA NIH HHS United States
U01 HG004436 NHGRI NIH HHS United States
U01 HG004738 NHGRI NIH HHS United States
U01 NS069208 NINDS NIH HHS United States
UL1 TR000448 NCATS NIH HHS United States
UL1RR024992 NCRR NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
CHRNA3
CHRNA5
CHRNB4
meta-analysis
nicotine
smoke
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Age of Onset
Cotinine metabolism
Female metabolism
Genetic Loci genetics
Genetic Predisposition to Disease genetics
Humans genetics
Internationality genetics
Linkage Disequilibrium genetics
Male genetics
Multigene Family genetics
Nerve Tissue Proteins genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
Receptors, Nicotinic genetics
Smoking genetics
Tobacco Use Disorder genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 CHRNA5 protein, human
0 CHRNB4 protein, human
0 Nerve Tissue Proteins
0 Receptors, Nicotinic
0 nicotinic receptor subunit alpha3
K5161X06LL Cotinine
OTHER ID's
OTHERID SOURCE
NIHMS538239 NLM
PMC3947535 NLM