Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.
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.
Hartz, SM; Short, SE; Saccone, NL; Culverhouse, R; Chen, L; Schwantes-An, T-H; 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, L-P; 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, B-Z; Aggen, SH; Balmforth, AJ; Baumeister, SE; Beaty, T; Bennett, S; Bergen, AW; Boyd, HA; Broms, U; Campbell, H; Chatterjee, N; Chen, J; Cheng, Y-C; 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, M-T; 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, M-R; 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, H-E; 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
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