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. DataExtraction: Uniform statistical analysis scripts were runlocally. Startingwith94 050ever-smokersfrom43studies, 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 heavyvs 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.
Original language | English |
---|---|
Pages (from-to) | 854-861 |
Number of pages | 8 |
Journal | Archives of General Psychiatry |
Volume | 69 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2012 |
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Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers. / Hartz, Sarah M.; Short, Susan E.; Saccone, Nancy L.; Culverhouse, Robert; Chen, Li Shiun; Schwantes-An, Tae Hwi; Coon, Hilary; Han, Younghun; Stephens, Sarah H.; Sun, Juzhong; Chen, Xiangning; Ducci, Francesca; Dueker, Nicole; Franceschini, Nora; Frank, Josef; Geller, Frank; Guobjartsson, Daniel; Hansel, Nadia N.; Jiang, Chenhui; Keskitalo-Vuokko, Kaisu; Liu, Zhen; Lyytikäinen, Leo Pekka; Michel, Martha; Rawal, Rajesh; Rosenberger, Albert; Scheet, Paul; Shaffer, John R.; Teumer, Alexander; Thompson, John R.; Vink, Jacqueline M.; Vogelzangs, Nicole; Wenzlaff, Angela S.; Wheeler, William; Xiao, Xiangjun; Yang, Bao Zhu; Aggen, Steven H.; Balmforth, Anthony J.; Baumeister, Sebastian E.; Beaty, Terri; Bennett, Siiri; Bergen, Andrew W.; Boyd, Heather A.; Broms, Ulla; Campbell, Harry; Chatterjee, Nilanjan; Chen, Jingchun; Cheng, Yu Ching; Cichon, Sven; Couper, David; Cucca, Francesco; Dick, Danielle M.; Foroud, Tatiana; Furberg, Helena; Giegling, Ina; Gu, Fangyi; Hall, Alistair S.; Hällfors, Jenni; Han, Shizhong; Hartmann, Annette M.; Hayward, Caroline; Heikkilä, Kauko; Hewitt, John K.; Hottenga, Jouke Jan; Jensen, Majken K.; Jousilahti, Pekka; Kaakinen, Marika; Kittner, Steven J.; Konte, Bettina; Korhonen, Tellervo; Landi, Maria Teresa; Laatikainen, Tiina; Leppert, Mark; Levy, Steven M.; Mathias, Rasika A.; McNeil, Daniel W.; Medland, Sarah E.; Montgomery, Grant W.; Muley, Thomas; Murray, Tanda; Nauck, Matthias; North, Kari; Pergadia, Michele; Polasek, Ozren; Ramos, Erin M.; Ripatti, Samuli; Risch, Angela; Ruczinski, Ingo; Rudan, Igor; Salomaa, Veikko; Schlessinger, David; Styrkársdóttir, Unnur; Terracciano, Antonio; Uda, Manuela; Willemsen, Gonneke; Wu, Xifeng; Abecasis, Goncalo; Barnes, Kathleen; Bickeböller, Heike; Boerwinkle, Eric; Boomsma, Dorret I.; Caporaso, Neil; Duan, Jubao; Edenberg, Howard J.; Francks, Clyde; Gejman, Pablo V.; Gelernter, Joel; Grabe, Hans Jörgen; Hops, Hyman; Jarvelin, Marjo Riitta; Viikari, Jorma; Kähönen, Mika; Kendler, Kenneth S.; Lehtimäki, Terho; Levinson, Douglas F.; Marazita, Mary L.; Marchini, Jonathan; Melbye, Mads; Mitchell, Braxton D.; Murray, Jeffrey C.; Nöthen, Markus M.; Penninx, Brenda W.; Raitakari, Olli; Rietschel, Marcella; Rujescu, Dan; Samani, Nilesh J.; Sanders, Alan R.; Schwartz, Ann G.; Shete, Sanjay; Shi, Jianxin; Spitz, Margaret; Stefansson, Kari; Swan, Gary E.; Thorgeirsson, Thorgeir; Völzke, Henry; Wei, Qingyi; Wichmann, H. Erich; Amos, Christopher I.; Breslau, Naomi; Cannon, Dale S.; Ehringer, Marissa; Grucza, Richard; Hatsukami, Dorothy; Heath, Andrew; Johnson, Eric O.; Kaprio, Jaakko; Madden, Pamela; Martin, Nicholas G.; Stevens, Victoria L.; Stitzel, Jerry A.; Weiss, Robert B.; Kraft, Peter; Bierut, Laura J.
In: Archives of General Psychiatry, Vol. 69, No. 8, 08.2012, p. 854-861.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers
AU - Hartz, Sarah M.
AU - Short, Susan E.
AU - Saccone, Nancy L.
AU - Culverhouse, Robert
AU - Chen, Li Shiun
AU - Schwantes-An, Tae Hwi
AU - Coon, Hilary
AU - Han, Younghun
AU - Stephens, Sarah H.
AU - Sun, Juzhong
AU - Chen, Xiangning
AU - Ducci, Francesca
AU - Dueker, Nicole
AU - Franceschini, Nora
AU - Frank, Josef
AU - Geller, Frank
AU - Guobjartsson, Daniel
AU - Hansel, Nadia N.
AU - Jiang, Chenhui
AU - Keskitalo-Vuokko, Kaisu
AU - Liu, Zhen
AU - Lyytikäinen, Leo Pekka
AU - Michel, Martha
AU - Rawal, Rajesh
AU - Rosenberger, Albert
AU - Scheet, Paul
AU - Shaffer, John R.
AU - Teumer, Alexander
AU - Thompson, John R.
AU - Vink, Jacqueline M.
AU - Vogelzangs, Nicole
AU - Wenzlaff, Angela S.
AU - Wheeler, William
AU - Xiao, Xiangjun
AU - Yang, Bao Zhu
AU - Aggen, Steven H.
AU - Balmforth, Anthony J.
AU - Baumeister, Sebastian E.
AU - Beaty, Terri
AU - Bennett, Siiri
AU - Bergen, Andrew W.
AU - Boyd, Heather A.
AU - Broms, Ulla
AU - Campbell, Harry
AU - Chatterjee, Nilanjan
AU - Chen, Jingchun
AU - Cheng, Yu Ching
AU - Cichon, Sven
AU - Couper, David
AU - Cucca, Francesco
AU - Dick, Danielle M.
AU - Foroud, Tatiana
AU - Furberg, Helena
AU - Giegling, Ina
AU - Gu, Fangyi
AU - Hall, Alistair S.
AU - Hällfors, Jenni
AU - Han, Shizhong
AU - Hartmann, Annette M.
AU - Hayward, Caroline
AU - Heikkilä, Kauko
AU - Hewitt, John K.
AU - Hottenga, Jouke Jan
AU - Jensen, Majken K.
AU - Jousilahti, Pekka
AU - Kaakinen, Marika
AU - Kittner, Steven J.
AU - Konte, Bettina
AU - Korhonen, Tellervo
AU - Landi, Maria Teresa
AU - Laatikainen, Tiina
AU - Leppert, Mark
AU - Levy, Steven M.
AU - Mathias, Rasika A.
AU - McNeil, Daniel W.
AU - Medland, Sarah E.
AU - Montgomery, Grant W.
AU - Muley, Thomas
AU - Murray, Tanda
AU - Nauck, Matthias
AU - North, Kari
AU - Pergadia, Michele
AU - Polasek, Ozren
AU - Ramos, Erin M.
AU - Ripatti, Samuli
AU - Risch, Angela
AU - Ruczinski, Ingo
AU - Rudan, Igor
AU - Salomaa, Veikko
AU - Schlessinger, David
AU - Styrkársdóttir, Unnur
AU - Terracciano, Antonio
AU - Uda, Manuela
AU - Willemsen, Gonneke
AU - Wu, Xifeng
AU - Abecasis, Goncalo
AU - Barnes, Kathleen
AU - Bickeböller, Heike
AU - Boerwinkle, Eric
AU - Boomsma, Dorret I.
AU - Caporaso, Neil
AU - Duan, Jubao
AU - Edenberg, Howard J.
AU - Francks, Clyde
AU - Gejman, Pablo V.
AU - Gelernter, Joel
AU - Grabe, Hans Jörgen
AU - Hops, Hyman
AU - Jarvelin, Marjo Riitta
AU - Viikari, Jorma
AU - Kähönen, Mika
AU - Kendler, Kenneth S.
AU - Lehtimäki, Terho
AU - Levinson, Douglas F.
AU - Marazita, Mary L.
AU - Marchini, Jonathan
AU - Melbye, Mads
AU - Mitchell, Braxton D.
AU - Murray, Jeffrey C.
AU - Nöthen, Markus M.
AU - Penninx, Brenda W.
AU - Raitakari, Olli
AU - Rietschel, Marcella
AU - Rujescu, Dan
AU - Samani, Nilesh J.
AU - Sanders, Alan R.
AU - Schwartz, Ann G.
AU - Shete, Sanjay
AU - Shi, Jianxin
AU - Spitz, Margaret
AU - Stefansson, Kari
AU - Swan, Gary E.
AU - Thorgeirsson, Thorgeir
AU - Völzke, Henry
AU - Wei, Qingyi
AU - Wichmann, H. Erich
AU - Amos, Christopher I.
AU - Breslau, Naomi
AU - Cannon, Dale S.
AU - Ehringer, Marissa
AU - Grucza, Richard
AU - Hatsukami, Dorothy
AU - Heath, Andrew
AU - Johnson, Eric O.
AU - Kaprio, Jaakko
AU - Madden, Pamela
AU - Martin, Nicholas G.
AU - Stevens, Victoria L.
AU - Stitzel, Jerry A.
AU - Weiss, Robert B.
AU - Kraft, Peter
AU - Bierut, Laura J.
N1 - Copyright: Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/8
Y1 - 2012/8
N2 - 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. Startingwith94 050ever-smokersfrom43studies, 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 heavyvs 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.
AB - 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. Startingwith94 050ever-smokersfrom43studies, 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 heavyvs 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.
UR - http://www.scopus.com/inward/record.url?scp=84865562672&partnerID=8YFLogxK
U2 - 10.1001/archgenpsychiatry.2012.124
DO - 10.1001/archgenpsychiatry.2012.124
M3 - Article
C2 - 22868939
AN - SCOPUS:84865562672
VL - 69
SP - 854
EP - 861
JO - Archives of General Psychiatry
JF - Archives of General Psychiatry
SN - 0003-990X
IS - 8
ER -