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Title: Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.
Authors: Hartz SM,  Short SE,  Saccone NL,  Culverhouse R,  Chen L,  Schwantes-An TH,  Coon H,  Han Y,  Stephens SH,  Sun J,  Chen X,  Ducci F,  Dueker N,  Franceschini N,  Frank J,  Geller F,  Gubjartsson D,  Hansel NN,  Jiang C,  Keskitalo-Vuokko K,  Liu Z,  Lyytikäinen LP,  Michel M,  Rawal R,  Rosenberger A,  Scheet P,  Shaffer JR,  Teumer A,  Thompson JR,  Vink JM,  Vogelzangs N,  Wenzlaff AS,  Wheeler W,  Xiao X,  Yang BZ,  Aggen SH,  Balmforth AJ,  Baumeister SE,  Beaty T,  Bennett S,  Bergen AW,  Boyd HA,  Broms U,  Campbell H,  Chatterjee N,  Chen J,  Cheng YC,  Cichon S,  Couper D,  Cucca F,  Dick DM,  Foroud T,  Furberg H,  Giegling I,  Gu F,  Hall AS,  Hällfors J,  Han S,  Hartmann AM,  Hayward C,  Heikkilä K,  Hewitt JK,  Hottenga JJ,  Jensen MK,  Jousilahti P,  Kaakinen M,  Kittner SJ,  Konte B,  Korhonen T,  Landi MT,  Laatikainen T,  Leppert M,  Levy SM,  Mathias RA,  McNeil DW,  Medland SE,  Montgomery GW,  Muley T,  Murray T,  Nauck M,  North K,  Pergadia M,  Polasek O,  Ramos EM,  Ripatti S,  Risch A,  Ruczinski I,  Rudan I,  Salomaa V,  Schlessinger D,  Styrkársdóttir U,  Terracciano A,  Uda M,  Willemsen G,  Wu X,  Abecasis G,  Barnes K,  Bickeböller H,  Boerwinkle E,  Boomsma DI,  Caporaso N,  Duan J,  Edenberg HJ,  Francks C,  Gejman PV,  Gelernter J,  Grabe HJ,  Hops H,  Jarvelin MR,  Viikari J,  Kähönen M,  Kendler KS,  Lehtimäki T,  Levinson DF,  Marazita ML,  Marchini J,  Melbye M,  Mitchell BD,  Murray JC,  Nöthen MM,  Penninx BW,  Raitakari O,  Rietschel M,  Rujescu D,  Samani NJ,  Sanders AR,  Schwartz AG,  Shete S,  Shi J,  Spitz M,  Stefansson K,  Swan GE,  Thorgeirsson T,  Völzke H,  Wei Q,  Wichmann HE,  Amos CI,  Breslau N,  Cannon DS,  Ehringer M,  Grucza R,  Hatsukami D,  Heath A,  Johnson EO,  Kaprio J,  Madden P,  Martin NG,  Stevens VL,  Stitzel JA,  Weiss RB,  Kraft P,  Bierut LJ
Journal: Arch Gen Psychiatry
Date: 2012 Aug
Branches: BB, GEB
PubMed ID: 22868939
PMC ID: PMC3482121
Abstract: CONTEXT: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. OBJECTIVE: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. DATA SOURCES: Primary data. STUDY SELECTION: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DATA EXTRACTION: 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. DATA SYNTHESIS: 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). CONCLUSION: These results highlight an increased genetic vulnerability to smoking in early-onset smokers.