Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers
Year: 2012
Type: article
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. 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.
Source: Archives of General Psychiatry
Authors: 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
Institutions: Washington University in St. Louis, Brown University, University of Utah, The University of Texas MD Anderson Cancer Center, University of Colorado Boulder, American Cancer Society, Virginia Commonwealth University, University of Pisa, King's College London, University of Maryland, Baltimore, University of North Carolina at Chapel Hill, Statens Serum Institut, deCODE Genetics (Iceland), Johns Hopkins University, Yale University, University of Helsinki, University of Oxford, SRI International, University of Göttingen, University of Pittsburgh, Universität Greifswald, University of Leicester, Vrije Universiteit Amsterdam, Wayne State University, University of Leeds, University of Washington, Finnish Institute for Health and Welfare, University of Edinburgh, National Institutes of Health, University of Bonn, National Academies of Sciences, Engineering, and Medicine, Indiana University Bloomington, Memorial Sloan Kettering Cancer Center, Ludwig-Maximilians-Universität München, Harvard University, University of Oulu, University of Iowa, West Virginia University, QIMR Berghofer Medical Research Institute, Heidelberg University, University of Split, German Cancer Research Center, University of Michigan, The University of Texas Health Science Center at Houston, University of Chicago, Max Planck Society, Oregon Research Institute, Imperial College London, University of Turku, Stanford University, Michigan State University, University of Minnesota, RTI International
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Andrew W. Mellon Foundation, Helsingin Yliopisto, National Alliance for Research on Schizophrenia and Depression, Wellcome Trust, National Institute for Health and Care Research, Deutsche Forschungsgemeinschaft, Tays, National Institutes of Health, U.S. Food and Drug Administration, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, National Center for Research Resources, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1034519783, G1054787755, G1064084138, G1066031372, G1083756078, G128083951, The Genetics of Vulnerability to Nicotine Addictions, G1425089079, G1449130676, G1535984833, G1567724564, THE AGES STUDY - THE REYKJAVIK STUDY OF HEALTHY AGING FOR THE NEW MILLENUM, G1691445938, G1794460117, G1826970460, Variants in CHRNA5/CHRNA3/CHRNB4 and nicotine dependence, Genetic Epidemiology of Lung Cancer, G1955273565, G205508870, G213398903, G2149630760, G2196166416, G2202404319, G2252333647, G2447083100, G2481876672, G250924255, G2561471519, DIAGNOSTIC CENTER FOR LINKAGE STUDIES OF SCHIZOPHRENIA, G2763219833, G3059684269, G3120785097, G3150776324, G3193254293, G3225162496, Molecular Genetics of Schizophrenia, Washington University Institute of Clinical and Translational Sciences, G3344726377, G34130399, G3453310768, G3453796565, G355565238, G364003555, G370871742, G3754093989, G3799582765, G3928017157, G3995976717, G407586344, G4103065728, G412057792, G413336477, G420024314, G425717312, Factors Contributing to Oral Health Disparities in Appalachia, G4418141037, Genetics of Alcohol Dependence in African-Americans, Genome Wide Association Coordinating Center, HUMAN GENETIC VARIATION IN SMOKING AND ADDICTION RISK, G4670284399, G4701672160, G4764582563, Transdisciplinary Research in Cancer of the Lung (TRICL), G4828408400, G4830326220, G490693365, G4961140939, G513541458, DIAGNOSTIC CENTER FOR SCHIZOPHRENIA LINKAGE STUDIES, Genes contributing for nicotine dependence in humans, SEER RRSS #4: Cancer in Arab American Estimating Rates and Fostering Research, Mapping Genes for comorbidity of SUDs and Depression, G5303213021, G55962079, G573982542, G5743592490, G577570207, Genetic Risk to Stroke in Smokers and Nonsmokers in Two Ethnic Groups, G599775046, Therapeutic competition among diseases in elders: Frequency and outcomes, G6129226368, Basic Research in Personality: Molecular Genetics of Personality, G6150611542, Genetics of Opioid Dependence, Molecular Genetics of Schizophrenia, G6348904714, R24 Population Center Grant, An NCRR Center for High Throughput SNP Genotyping and Analysis, Genetics of Alcohol Dependence in American Populations, G6587255222, G697048246, Mid-Atlantic Nutrition Obesity Research Center, G697852961, Understanding the genetic basis of common human diseases: core funding for the Wellcome Trust Centre for Human Genetics., Genome-wide Association Study of Schizophrenia, Washington University Institute of Clinical and Translational Sciences, Pharmacogenetics of Nicotine Addiction Treatment, G7423759087, G7472280766, G747687783, G7645038227, Washington University Institute of Clinical and Translational Sciences (KL2), G7704018871, Psychometric and Genetic Assessments of Substance Use, Washington University Institute of Clinical and Translational Sciences (UL1), G792207106, G8267674335, Genetics of Cocaine Dependence, G8453940506, G858805679, Genetics of Early Onset-Stroke, Molecular Genetics of Schizophrenia, The Genetic Epidemiology of Nicotine Dependence, The NINDS International Stroke Genetics Consortium Study, G8945614085, G899224547, G9000024769, G9000025954, G9000054071, G9000100968, G9000134904, G9000176579, G9000192317, G9000273886, EARLY INTERVENTION/CHRONIC OBSTRUCTIVE PULMONARY DISEASE
OpenAlex ID: W2098545747