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., 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., Lyytikäinen, L., 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., 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., Cichon, S., Couper, D., Cucca, F., Dick, D. M., Foroud, T., Furberg, H., Giegling, I., Gu, F., Hall, A. S., Hällfors, J., Han, S., Hartmann, A. M., Hayward, C., Heikkilä, K., Hewitt, J. K., Hottenga, J. J., Jensen, M. K., Jousilahti, P., Kaakinen, M., Kittner, S. J., Konte, B., Korhonen, T., Landi, M., Laatikainen, T., Leppert, M., Levy, S. M., Mathias, R. A., McNeil, D. W., Medland, S. E., Montgomery, G. W., Muley, T., Murray, T., Nauck, M., North, K., Pergadia, M., Polasek, O., Ramos, E. M., 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. I., Caporaso, N., Duan, J., Edenberg, H. J., Francks, C., Gejman, P. V., Gelernter, J., Grabe, H. J., Hops, H., Jarvelin, M., Viikari, J., Kähönen, M., Kendler, K. S., Lehtimäki, T., Levinson, D. F., Marazita, M. L., Marchini, J., Melbye, M., Mitchell, B. D., Murray, J. C., Nöthen, M. M., Penninx, B. W., Raitakari, O., Rietschel, M., Rujescu, D., Samani, N. J., Sanders, A. R., Schwartz, A. G., Shete, S., Shi, J., Spitz, M., Stefansson, K., Swan, G. E., Thorgeirsson, T., Völzke, H., Wei, Q., Wichmann, H. E., Amos, C. I., Breslau, N., Cannon, D. S., Ehringer, M., Grucza, R., Hatsukami, D., Heath, A., Johnson, E. O., Kaprio, J., Madden, P., Martin, N. G., Stevens, V. L., Stitzel, J. A., Weiss, R. B., Kraft, P., & Bierut, L. J. Archives of General Psychiatry, 69(8):854–860, 2012.
Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers [link]Paper  doi  abstract   bibtex   
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.
@article{hartz_increased_2012,
	title = {Increased {Genetic} {Vulnerability} to {Smoking} at {CHRNA5} in {Early}-{Onset} {Smokers}},
	volume = {69},
	issn = {0003-990X},
	url = {https://doi.org/10.1001/archgenpsychiatry.2012.124},
	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.},
	number = {8},
	urldate = {2020-11-10},
	journal = {Archives of General Psychiatry},
	author = {Hartz, Sarah M. and Short, Susan E. and Saccone, Nancy L. and Culverhouse, Robert and Chen, LiShiun and Schwantes-An, Tae-Hwi and Coon, Hilary and Han, Younghun and Stephens, Sarah H. and Sun, Juzhong and Chen, Xiangning and Ducci, Francesca and Dueker, Nicole and Franceschini, Nora and Frank, Josef and Geller, Frank and Gubjartsson, Daniel and Hansel, Nadia N. and Jiang, Chenhui and Keskitalo-Vuokko, Kaisu and Liu, Zhen and Lyytikäinen, Leo-Pekka and Michel, Martha and Rawal, Rajesh and Rosenberger, Albert and Scheet, Paul and Shaffer, John R. and Teumer, Alexander and Thompson, John R. and Vink, Jacqueline M. and Vogelzangs, Nicole and Wenzlaff, Angela S. and Wheeler, William and Xiao, Xiangjun and Yang, Bao-Zhu and Aggen, Steven H. and Balmforth, Anthony J. and Baumeister, Sebastian E. and Beaty, Terri and Bennett, Siiri and Bergen, Andrew W. and Boyd, Heather A. and Broms, Ulla and Campbell, Harry and Chatterjee, Nilanjan and Chen, Jingchun and Cheng, Yu-Ching and Cichon, Sven and Couper, David and Cucca, Francesco and Dick, Danielle M. and Foroud, Tatiana and Furberg, Helena and Giegling, Ina and Gu, Fangyi and Hall, Alistair S. and Hällfors, Jenni and Han, Shizhong and Hartmann, Annette M. and Hayward, Caroline and Heikkilä, Kauko and Hewitt, John K. and Hottenga, Jouke Jan and Jensen, Majken K. and Jousilahti, Pekka and Kaakinen, Marika and Kittner, Steven J. and Konte, Bettina and Korhonen, Tellervo and Landi, Maria-Teresa and Laatikainen, Tiina and Leppert, Mark and Levy, Steven M. and Mathias, Rasika A. and McNeil, Daniel W. and Medland, Sarah E. and Montgomery, Grant W. and Muley, Thomas and Murray, Tanda and Nauck, Matthias and North, Kari and Pergadia, Michele and Polasek, Ozren and Ramos, Erin M. and Ripatti, Samuli and Risch, Angela and Ruczinski, Ingo and Rudan, Igor and Salomaa, Veikko and Schlessinger, David and Styrkársdóttir, Unnur and Terracciano, Antonio and Uda, Manuela and Willemsen, Gonneke and Wu, Xifeng and Abecasis, Goncalo and Barnes, Kathleen and Bickeböller, Heike and Boerwinkle, Eric and Boomsma, Dorret I. and Caporaso, Neil and Duan, Jubao and Edenberg, Howard J. and Francks, Clyde and Gejman, Pablo V. and Gelernter, Joel and Grabe, Hans Jörgen and Hops, Hyman and Jarvelin, Marjo-Riitta and Viikari, Jorma and Kähönen, Mika and Kendler, Kenneth S. and Lehtimäki, Terho and Levinson, Douglas F. and Marazita, Mary L. and Marchini, Jonathan and Melbye, Mads and Mitchell, Braxton D. and Murray, Jeffrey C. and Nöthen, Markus M. and Penninx, Brenda W. and Raitakari, Olli and Rietschel, Marcella and Rujescu, Dan and Samani, Nilesh J. and Sanders, Alan R. and Schwartz, Ann G. and Shete, Sanjay and Shi, Jianxin and Spitz, Margaret and Stefansson, Kari and Swan, Gary E. and Thorgeirsson, Thorgeir and Völzke, Henry and Wei, Qingyi and Wichmann, H. Erich and Amos, Christopher I. and Breslau, Naomi and Cannon, Dale S. and Ehringer, Marissa and Grucza, Richard and Hatsukami, Dorothy and Heath, Andrew and Johnson, Eric O. and Kaprio, Jaakko and Madden, Pamela and Martin, Nicholas G. and Stevens, Victoria L. and Stitzel, Jerry A. and Weiss, Robert B. and Kraft, Peter and Bierut, Laura J.},
	year = {2012},
	pages = {854--860},
}
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