Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers

Hartz, S.; Short, S.; Saccone, N.; Culverhouse, R.; Chen, L.; Schwantes-An, T.; Coon, H.; Han, Y.; Stephens, S.; Sun, J.; Chen, X.; Ducci, F.; Dueker, N.; Franceschini, N.; Frank, J.; Geller, F.; Guobjartsson, D.; Hansel, N.; Jiang, C.; Keskitalo-Vuokko, K.; Liu, Z.; Lyytikäinen, L.; Michel, M.; Rawal, R.; Rosenberger, A.; Scheet, P.; Shaffer, J.; Teumer, A.; Thompson, J.; Vink, J.; Vogelzangs, N.; Wenzlaff, A.; Wheeler, W.; Xiao, X.; Yang, B.; Aggen, S.; Balmforth, A.; Baumeister, S.; Beaty, T.; Bennett, S.; Bergen, A.; Boyd, H.; Broms, U.; Campbell, H.; Chatterjee, N.; Chen, J.; Cheng, Y.; Cichon, S.; Couper, D.; Cucca, F.; Dick, D.; Foroud, T.; Furberg, H.; Giegling, I.; Gu, F.; Hall, A.; Hällfors, J.; Han, S.; Hartmann, A.; Hayward, C.; Heikkilä, K.; Hewitt, J.; Hottenga, J.; Jensen, M.; Jousilahti, P.; Kaakinen, M.; Kittner, S.; Konte, B.; Korhonen, T.; Landi, M.; Laatikainen, T.; Leppert, M.; Levy, S.; Mathias, R.; Mcneil, D.; Medland, S.; Montgomery, G.; Muley, T.; Murray, T.; Nauck, M.; North, K.; Pergadia, M.; Polasek, O.; Ramos, E.; 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, D.; Caporaso, N.; Duan, J.; Edenberg, H.; Francks, C.; Gejman, P.; Gelernter, J.; Grabe, H.; Hops, H.; Jarvelin, M.; Viikari, J.; Kähönen, M.; Kendler, K.; Lehtimäki, T.; Levinson, D.; Marazita, M.; Marchini, J.; Melbye, M.; Mitchell, B.; Murray, J.; Nöthen, M.; Penninx, B.; Raitakari, O.; Rietschel, M.; Rujescu, D.; Samani, N.; Sanders, A.; Schwartz, A.; Shete, S.; Shi, J.; Spitz, M.; Stefansson, K.; Swan, G.; Thorgeirsson, T.; Völzke, H.; Wei, Q.; Wichmann, H.; Amos, C.; Breslau, N.; Cannon, D.; Ehringer, M.; Grucza, R.; Hatsukami, D.; Heath, A.; Johnson, E.; Kaprio, J.; Madden, P.; Martin, N.; Stevens, V.; Stitzel, J.; Weiss, R.; Kraft, P.; Bierut, L.

doi:10.1001/archgenpsychiatry.2012.124

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. DataExtraction: Uniform statistical analysis scripts were runlocally. 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, re-ducing 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 ther s16969968 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.

Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers / Hartz, S.; Short, S.; Saccone, N.; Culverhouse, R.; Chen, L.; Schwantes-An, T.; Coon, H.; Han, Y.; Stephens, S.; Sun, J.; Chen, X.; Ducci, F.; Dueker, N.; Franceschini, N.; Frank, J.; Geller, F.; Guobjartsson, D.; Hansel, N.; Jiang, C.; Keskitalo-Vuokko, K.; Liu, Z.; Lyytikäinen, L.; Michel, M.; Rawal, R.; Rosenberger, A.; Scheet, P.; Shaffer, J.; Teumer, A.; Thompson, J.; Vink, J.; Vogelzangs, N.; Wenzlaff, A.; Wheeler, W.; Xiao, X.; Yang, B.; Aggen, S.; Balmforth, A.; Baumeister, S.; Beaty, T.; Bennett, S.; Bergen, A.; Boyd, H.; Broms, U.; Campbell, H.; Chatterjee, N.; Chen, J.; Cheng, Y.; Cichon, S.; Couper, D.; Cucca, F.; Dick, D.; Foroud, T.; Furberg, H.; Giegling, I.; Gu, F.; Hall, A.; Hällfors, J.; Han, S.; Hartmann, A.; Hayward, C.; Heikkilä, K.; Hewitt, J.; Hottenga, J.; Jensen, M.; Jousilahti, P.; Kaakinen, M.; Kittner, S.; Konte, B.; Korhonen, T.; Landi, M.; Laatikainen, T.; Leppert, M.; Levy, S.; Mathias, R.; Mcneil, D.; Medland, S.; Montgomery, G.; Muley, T.; Murray, T.; Nauck, M.; North, K.; Pergadia, M.; Polasek, O.; Ramos, E.; 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, D.; Caporaso, N.; Duan, J.; Edenberg, H.; Francks, C.; Gejman, P.; Gelernter, J.; Grabe, H.; Hops, H.; Jarvelin, M.; Viikari, J.; Kähönen, M.; Kendler, K.; Lehtimäki, T.; Levinson, D.; Marazita, M.; Marchini, J.; Melbye, M.; Mitchell, B.; Murray, J.; Nöthen, M.; Penninx, B.; Raitakari, O.; Rietschel, M.; Rujescu, D.; Samani, N.; Sanders, A.; Schwartz, A.; Shete, S.; Shi, J.; Spitz, M.; Stefansson, K.; Swan, G.; Thorgeirsson, T.; Völzke, H.; Wei, Q.; Wichmann, H.; Amos, C.; Breslau, N.; Cannon, D.; Ehringer, M.; Grucza, R.; Hatsukami, D.; Heath, A.; Johnson, E.; Kaprio, J.; Madden, P.; Martin, N.; Stevens, V.; Stitzel, J.; Weiss, R.; Kraft, P.; Bierut, L.. - In: ARCHIVES OF GENERAL PSYCHIATRY. - ISSN 0003-990X. - 69:8(2012), pp. 854-861. [10.1001/archgenpsychiatry.2012.124]