早期吸烟者 CHRNA5 基因对吸烟的易感性增加。

Sarah M Hartz, Susan E Short, Nancy L Saccone, Robert Culverhouse, LiShiun Chen, Tae-Hwi Schwantes-An, Hilary Coon, Younghun Han, Sarah H Stephens, Juzhong Sun, Xiangning Chen, Francesca Ducci, Nicole Dueker, Nora Franceschini, Josef Frank, Frank Geller, Daniel Gubjartsson, Nadia N Hansel, Chenhui Jiang, Kaisu Keskitalo-Vuokko, Zhen Liu, Leo-Pekka Lyytikäinen, Martha Michel, Rajesh Rawal, Albert Rosenberger, Paul Scheet, John R Shaffer, Alexander Teumer, John R Thompson, Jacqueline M Vink, Nicole Vogelzangs, Angela S Wenzlaff, William Wheeler, Xiangjun Xiao, Bao-Zhu Yang, Steven H Aggen, Anthony J Balmforth, Sebastian E Baumeister, Terri Beaty, Siiri Bennett, Andrew W Bergen, Heather A Boyd, Ulla Broms, Harry Campbell, Nilanjan Chatterjee, Jingchun Chen, Yu-Ching Cheng, Sven Cichon, David Couper, Francesco Cucca, Danielle M Dick, Tatiana Foroud, Helena Furberg, Ina Giegling, Fangyi Gu, Alistair S Hall, Jenni Hällfors, Shizhong Han, Annette M Hartmann, Caroline Hayward, Kauko Heikkilä, John K Hewitt, Jouke Jan Hottenga, Majken K Jensen, Pekka Jousilahti, Marika Kaakinen, Steven J Kittner, Bettina Konte, Tellervo Korhonen, Maria-Teresa Landi, Tiina Laatikainen, Mark Leppert, Steven M Levy, Rasika A Mathias, Daniel W McNeil, Sarah E Medland, Grant W Montgomery, Thomas Muley, Tanda Murray, Matthias Nauck, Kari North, Michele Pergadia, Ozren Polasek, Erin M Ramos, Samuli Ripatti, Angela Risch, Ingo Ruczinski, Igor Rudan, Veikko Salomaa, David Schlessinger, Unnur Styrkársdóttir, Antonio Terracciano, Manuela Uda, Gonneke Willemsen, Xifeng Wu, Goncalo Abecasis, Kathleen Barnes, Heike Bickeböller, Eric Boerwinkle, Dorret I Boomsma, Neil Caporaso, Jubao Duan, Howard J Edenberg, Clyde Francks, Pablo V Gejman, Joel Gelernter, Hans Jörgen Grabe, Hyman Hops, Marjo-Riitta Jarvelin, Jorma Viikari, Mika Kähönen, Kenneth S Kendler, Terho Lehtimäki, Douglas F Levinson, Mary L Marazita, Jonathan Marchini, Mads Melbye, Braxton D Mitchell, Jeffrey C Murray, Markus M Nöthen, Brenda W Penninx, Olli Raitakari, Marcella Rietschel, Dan Rujescu, Nilesh J Samani, Alan R Sanders, Ann G Schwartz, Sanjay Shete, Jianxin Shi, Margaret Spitz, Kari Stefansson, Gary E Swan, Thorgeir Thorgeirsson, Henry Völzke, Qingyi Wei, H-Erich Wichmann, Christopher I Amos, Naomi Breslau, Dale S Cannon, Marissa Ehringer, Richard Grucza, Dorothy Hatsukami, Andrew Heath, Eric O Johnson, Jaakko Kaprio, Pamela Madden, Nicholas G Martin, Victoria L Stevens, Jerry A Stitzel, Robert B Weiss, Peter Kraft, Laura J Bierut
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引用次数: 0

摘要

背景:最近的研究表明,每天吸烟量(CPD)与 CHRNA5 中的非同义单核苷酸多态性 rs16969968 之间存在关联:目的:确定 rs16969968 与吸烟的关系是否会因开始经常吸烟的年龄而改变:研究选择:数据提取:在本地运行统一的统计分析脚本。从 43 项研究中的 94,050 名曾经吸烟者开始,我们提取了具有发病年龄信息的重度吸烟者(CPD >20)和轻度吸烟者(CPD ≤10),将样本量减少到 33,348 人。将每项研究分为早发吸烟者(发病年龄≤16 岁)和晚发吸烟者(发病年龄大于 16 岁),并对每个分层计算重度吸烟与轻度吸烟的 rs16969968 基因型的逻辑回归。在每个发病年龄层内进行 Meta 分析:数据综述:与风险等位基因携带者中的晚期吸烟者(OR = 1.27; 95% CI, 1.21-1.33, n = 19,505)相比,rs16969968的1个风险等位基因携带者中的早期吸烟者在成年后成为重度吸烟者的几率明显更高(几率比[OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843)(P = .01):这些结果凸显了早发性吸烟者的遗传易感性增加。
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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.

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Archives of general psychiatry
Archives of general psychiatry 医学-精神病学
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