Journal Article

PreJuSER-22402

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers

Hartz, S. M. ; Short, S. E. ; Saccone, N. L. ; Culverhouse, R. ; Chen, L. ; Schwantes-An, T. H. ; Coon, H. ; Han, Y. ; Stephens, S. H. ; Sun, J. ; Chen, X. ; Ducci, F. ; Dueker, N. ; Franceschini, N. ; Frank, J. ; Geller, F. ; Gubjartsson, D. ; Hansel, N. N. ; Jiang, C. ; Keskitalo-Vuokko, K. ; Liu, Z. ; Lyytikainen, L. P. ; Michel, M. ; Rawal, R. ; Rosenberger, A. ; Scheet, P. ; Shaffer, J. R. ; Teumer, A. ; Thompson, J. R. ; Vink, J. M. ; Vogelzangs, N. ; Wenzlaff, A. S. ; Wheeler, W. ; Xiao, X. ; Yang, B. Z. ; Aggen, S. H. ; Balmforth, A. J. ; Baumeister, S. E. ; Beaty, T. ; Bennett, S. ; Bergen, A. W. ; Boyd, H. A. ; Broms, U. ; Campbell, H. ; Chatterjee, N. ; Chen, J. ; Cheng, Y. C. ; Cichon, S.FZJ* ; et, a.

2012
AMA Chicago, Ill.

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Please use a persistent id in citations: doi:10.1001/archgenpsychiatry.2012.124

Abstract: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968.To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking.Primary data.Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy.Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum.Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01).These results highlight an increased genetic vulnerability to smoking in early-onset smokers.

Keyword(s): Adolescent (MeSH) ; Adolescent Development: drug effects (MeSH) ; Adult (MeSH) ; Age of Onset (MeSH) ; Europe: epidemiology (MeSH) ; Female (MeSH) ; Gene-Environment Interaction (MeSH) ; Genetic Association Studies (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Nerve Tissue Proteins: genetics (MeSH) ; Nicotine: pharmacology (MeSH) ; Polymorphism, Single Nucleotide (MeSH) ; Receptors, Nicotinic: genetics (MeSH) ; Severity of Illness Index (MeSH) ; Smoking: epidemiology (MeSH) ; Smoking: genetics (MeSH) ; Tobacco Use Disorder: epidemiology (MeSH) ; Tobacco Use Disorder: genetics (MeSH) ; Tobacco Use Disorder: psychology (MeSH) ; CHRNA5 protein, human ; Nerve Tissue Proteins ; Receptors, Nicotinic ; Nicotine ; J

Note: This study was supported by grants R01HL089651-01, U01-DE018903, N01-AG-1-2109, K01DA24758, N01-PC35145, N01-PC35146, N01-HR-46002, K07 CA118412, K02 AA018755, U10 AA008401, K01DA19498, K02DA021237, P01 CA089392, R01 MH59571, R01 MH61675, R01CA060691, R01CA060691, U01 MH79469, U01 MH79470, R01 AA017535, R01 AA11330, R01 DA12690, R01 DA12849, R01DA026911, R01DA25888, R01NS45012, R21DA027070, T32 MH014677, U01 HG004436, U01HG004438, U01 NS069208, U01HG004446, UL1RR024992, NIHDA12854, DA019951, R21DA033827, HHSN268200782096C, U01 HG004738, U01DA02830, R01 MH67257, R01 MH59588, R01 MH59565, R01 MH59587, R01 MH60870, R01 MH59566, R01 MH59586, R01 MH60879, R01 MH81800, U01 MH46276, MH46289, MH46318, U54 RR020278, R01 DA017932, and R01 DA03706 from the National Institutes of Health; the Intramural Research Program of the National Institutes of Health, National Institute on Aging; grant 7PT2000-2004 from the University of California Tobacco-Related Disease Research Program; Academy of Finland (project grants 104781 and 120315 and the Center of Excellence in Complex Disease Genetics); University Hospital Oulu; the European Commission; the European Commission's Sixth Framework Program, Integrated Project GENADDICT (LSHM-CT-2004-005166), and the Seventh Framework Program, Integrated Project ENGAGE (HEALTH-F4-2007-201413); Academy of Finland Center of Excellence in Complex Disease Genetics, Global Research Awards for Nicotine Dependence; SALVE program grant 129494; The Finnish Foundation for Cardiovascular Diseases; Alfried Krupp von Bohlen und Halbach-Stiftung; German Federal Ministry of Education and Research grants 01ZZ9603, 01ZZ0103, 01ZZ0403, NGNF-2, NGFNplus, IG MooDS: 01GS08144, and 01GS08147; Geestkracht programme of the Dutch Scientific Organization(ZON-MW grant 10-000-1002); matching funds from participating institutes; Center for Molecular and Systems Biology; the Genetic Association Information Network of the Foundation for the US National Institutes of Health, German Research Foundation (DFG: GR 1912/5-1); University of Helsinki Biomedical Graduate School; Medical Research Fund of Tampere University Hospital; National Institute for Health Research Academic Clinical Fellowship at the Division of Mental Health, St George's, University of London; NARSAD Young Investigator Award; Wellcome Trust; The Paul Michael Donovan Charitable Foundation; The Andrew W. Mellon Foundation; and The Mary Beryl Patch Turnbull Scholar Program.

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Contributing Institute(s):

1. Strukturelle und funktionelle Organisation des Gehirns (INM-1)

Research Program(s):

1. Funktion und Dysfunktion des Nervensystems (P33)

Appears in the scientific report 2012

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