Journal article
Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking
Genetic epidemiology, Vol.37(8), pp.846-859
12/2013
DOI: 10.1002/gepi.21760
PMCID: PMC3947535
PMID: 24186853
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.
Details
- Title: Subtitle
- Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking
- Creators
- Sarah H Stephens - Department of Epidemiology and Public Health, University of Maryland, Baltimore, Maryland, United States of AmericaSarah M HartzNicole R HoftNancy L SacconeRobin C CorleyJohn K HewittChristian J HopferNaomi BreslauHilary CoonXiangning ChenFrancesca DucciNicole DuekerNora FranceschiniJosef FrankYounghun HanNadia N HanselChenhui JiangTellervo KorhonenPenelope A LindJason LiuLeo-Pekka LyytikäinenMartha MichelJohn R ShafferSusan E ShortJuzhong SunAlexander TeumerJohn R ThompsonNicole VogelzangsJacqueline M VinkAngela WenzlaffWilliam WheelerBao-Zhu YangSteven H AggenAnthony J BalmforthSebastian E BaumeisterTerri H BeatyDaniel J BenjaminAndrew W BergenUlla BromsDavid CesariniNilanjan ChatterjeeJingchun ChenYu-Ching ChengSven CichonDavid CouperFrancesco CuccaDanielle DickTatiana ForoudHelena FurbergIna GieglingNathan A GillespieFangyi GuAlistair S HallJenni HällforsAnnette M HartmannKauko HeikkiläIan B HickieJouke Jan HottengaPekka JousilahtiMarika KaakinenMika KähönenPhilipp D KoellingerStephen KittnerBettina KonteMaria-Teresa LandiTiina LaatikainenMark LeppertSteven M LevyRasika A MathiasDaniel W McNeilSarah E MedlandGrant W MontgomeryTanda MurrayMatthias NauckKari E NorthPeter D ParéMichele PergadiaIngo RuczinskiVeikko SalomaaJorma ViikariGonneke WillemsenKathleen C BarnesEric BoerwinkleDorret I BoomsmaNeil CaporasoHoward J EdenbergClyde FrancksJoel GelernterHans Jörgen GrabeHyman HopsMarjo-Riitta JarvelinMagnus JohannessonKenneth S KendlerTerho LehtimäkiPatrik K E MagnussonMary L MarazitaJonathan MarchiniBraxton D MitchellMarkus M NöthenBrenda W PenninxOlli RaitakariMarcella RietschelDan RujescuNilesh J SamaniAnn G SchwartzSanjay SheteMargaret SpitzGary E SwanHenry VölzkeJuha VeijolaQingyi WeiChris AmosDale S CannonRichard GruczaDorothy HatsukamiAndrew HeathEric O JohnsonJaakko KaprioPamela MaddenNicholas G MartinVictoria L StevensPeter KraftLaura J BierutShizhong Han - Yale UniversityRobert B Weiss - University of Utah HospitalMarissa A Ehringer
- Resource Type
- Journal article
- Publication Details
- Genetic epidemiology, Vol.37(8), pp.846-859
- Publisher
- United States
- DOI
- 10.1002/gepi.21760
- PMID
- 24186853
- PMCID
- PMC3947535
- ISSN
- 1098-2272
- eISSN
- 1098-2272
- Grant note
- K02 DA021237 / NIDA NIH HHS R01 DA012854 / NIDA NIH HHS R01 NS045012 / NINDS NIH HHS R01 DA12690 / NIDA NIH HHS R01 AA013321 / NIAAA NIH HHS P60 DA011015 / NIDA NIH HHS KL2 RR024994 / NCRR NIH HHS K01 DA19498 / NIDA NIH HHS K08 DA032680 / NIDA NIH HHS R01 AA007535 / NIAAA NIH HHS UL1 TR000448 / NCATS NIH HHS 090532 / Wellcome Trust R01 AA11330 / NIAAA NIH HHS K01 DA019498 / NIDA NIH HHS U01 DA02830 / NIDA NIH HHS K05 AA017688 / NIAAA NIH HHS U01 HG004436 / NHGRI NIH HHS R01 DA026911 / NIDA NIH HHS 230374 / European Research Council R01 DE014899 / NIDCR NIH HHS K07 CA118412 / NCI NIH HHS R01 AA014041 / NIAAA NIH HHS P50 AA011998 / NIAAA NIH HHS U01 DA020830 / NIDA NIH HHS K01 DA24758 / NIDA NIH HHS P30 DK072488 / NIDDK NIH HHS R01 AA07535 / NIAAA NIH HHS R24 HD041020 / NICHD NIH HHS P30 DK-072488 / NIDDK NIH HHS P01 AG005842 / NIA NIH HHS N01-PC35146 / NCI NIH HHS K99R00 DA023549 / NIDA NIH HHS R01 DA021913 / NIDA NIH HHS UL1RR024992 / NCRR NIH HHS R01 AA14041 / NIAAA NIH HHS R21 DA027070 / NIDA NIH HHS R01 AA13320 / NIAAA NIH HHS R01 AA11998 / NIAAA NIH HHS R00 DA023549 / NIDA NIH HHS R01 AA07728 / NIAAA NIH HHS R01 NS45012 / NINDS NIH HHS R01 DA012690 / NIDA NIH HHS R01 CA060691 / NCI NIH HHS R01 DE12101 / NIDCR NIH HHS U01 NS069208 / NINDS NIH HHS R01 DA12854 / NIDA NIH HHS P30 CA016672 / NCI NIH HHS 284167 / European Research Council K01 DA024758 / NIDA NIH HHS K02 AA018755 / NIAAA NIH HHS R01 CA087895 / NCI NIH HHS N01-AG-1-2109 / NIA NIH HHS R01 AA013320 / NIAAA NIH HHS R01 CA87895 / NCI NIH HHS R01 AA017535 / NIAAA NIH HHS R01 HL089651 / NHLBI NIH HHS R01 DE012101 / NIDCR NIH HHS R01 DA012849 / NIDA NIH HHS R01 AA17688 / NIAAA NIH HHS T32 AG000186 / NIA NIH HHS R01 AA007728 / NIAAA NIH HHS R01 AA011330 / NIAAA NIH HHS R01AA13321 / NIAAA NIH HHS R01 DA03706 / NIDA NIH HHS U01 HG004738 / NHGRI NIH HHS KL2 TR000450 / NCATS NIH HHS UL1 RR024992 / NCRR NIH HHS P01 CA089392 / NCI NIH HHS R01HL089651-01 / NHLBI NIH HHS R01 DA12849 / NIDA NIH HHS
- Language
- English
- Date published
- 12/2013
- Academic Unit
- Preventive and Community Dentistry; Psychiatry; Epidemiology
- Record Identifier
- 9983917789602771
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