Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers
Open accessAbstract
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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CHRNA5 has been linked in several studies to smoking and various smoking risk factors.
“CHRNA5 has been linked in several studies to smoking and various smoking risk factors [53–57].”
From Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes (2022) · cites this paper as [55]
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- Authors
- Hartz, S. M., Short, S. E., Saccone, N. L., Culverhouse, R., Chen, L., Schwantes-An, T.-H., 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.-P., 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.-Z., 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.-C., 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.-T., 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.-R., 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.
- Affiliations
- Washington University in St. Louis (US)
- University of North Carolina at Chapel Hill (US)
- University of Pisa (IT)
- Statens Serum Institut (DK)
- Corresponding author
- Bierut, Laura J.
- ORCID
- Hartz, Sarah M.
- Short, Susan E.
- Saccone, Nancy L.
- Culverhouse, Robert
- Schwantes-An, Tae-Hwi
- Coon, Hilary
- Han, Younghun
- Sun, Juzhong
- Chen, Xiangning
- Dueker, Nicole
- Franceschini, Nora
- Frank, Josef
- Geller, Frank
- Hansel, Nadia N.
- Liu, Zhen
- Lyytikäinen, Leo-Pekka
- Rawal, Rajesh
- Rosenberger, Albert
- Scheet, Paul
- Shaffer, John R.
- Teumer, Alexander
- Vink, Jacqueline M.
- Vogelzangs, Nicole
- Wenzlaff, Angela S.
- Wheeler, William
- Xiao, Xiangjun
- Yang, Bao-Zhu
- Aggen, Steven H.
- Baumeister, Sebastian E.
- Beaty, Terri
- Bergen, Andrew W.
- Boyd, Heather A.
- 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
- Hewitt, John K.
- Hottenga, Jouke Jan
- Jensen, Majken K.
- Kaakinen, Marika
- Kittner, Steven J.
- Konte, Bettina
- Korhonen, Tellervo
- Laatikainen, Tiina
- Levy, Steven M.
- Mathias, Rasika A.
- McNeil, Daniel W.
- Medland, Sarah E.
- Montgomery, Grant W.
- Muley, Thomas
- Nauck, Matthias
- North, Kari
- 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
- Barnes, Kathleen
- Bickeböller, Heike
- Boerwinkle, Eric
- Boomsma, Dorret I.
- Caporaso, Neil
- Duan, Jubao
- Edenberg, Howard J.
- Francks, Clyde
- Gelernter, Joel
- Grabe, Hans Jörgen
- 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
- Swan, Gary E.
- Thorgeirsson, Thorgeir
- Völzke, Henry
- Wei, Qingyi
- Wichmann, H.-Erich
- Amos, Christopher I.
- 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.
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2012-08-01
- Volume
- 69
- Issue
- 8
- Pages
- 854
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC3482121
- OpenAlex
- W2098545747
- Cited by
- 75
- References
- 39
- Citations by year
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- FWCI
- 8.30
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- VU Research Portal (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Digital Library (submittedVersion)
- UnissResearch (Università degli Studi di Sassari) (submittedVersion)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Site cant be reached (submittedVersion)
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- MPG.PuRe (Max Planck Society) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Andrew W. Mellon Foundation
- Helsingin Yliopisto
- National Alliance for Research on Schizophrenia and Depression
- Wellcome Trust (090532)
- National Institute for Health and Care Research
- Deutsche Forschungsgemeinschaft (Gr1912/5‐1)
- Tays
- National Institutes of Health (N01-AG-1-2109, n01ag12100-57-0-2, KL2TR000450, N01-PC35145, n01pc35145-19-0-7, PC35145, 6u54rr020278-06, UL1TR000448, Z99 AG999999, TL1TR000449, 5u01ns069208-04, AA008401, CA089392, n01hr046002-024)
- U.S. Food and Drug Administration (R01 FD003706)
- National Institute on Alcohol Abuse and Alcoholism (K02AA018755, K05AA017688, R01AA017535, R01AA011330, U10AA008401)
- National Institute on Aging (N01-AG-12109, N01-AG012100, R03AG035146, ZIAAG000196)
- National Heart, Lung, and Blood Institute (N01 HR046002, R01HL089651)
- National Institute of Mental Health (U01MH046276, R01MH059566, U01MH046318, R01MH059571, R01MH060879, R01MH059565, MH46289, R01MH081800, MH46318, R01MH060870, U01MH046289, U01MH079469, R01MH061675, R01MH059586, R01MH059588, T32MH014677, R01MH067257, U01MH079470, R01MH059587)
- National Institute on Drug Abuse (R56DA012854, R21DA033827, DA 019951, R01DA003706, R21DA027070, U01 DA02830, K08DA032680, K01DA019498, DA12854, K08DA030398, R01DA026911, R01DA017932, K01DA024758, R01DA012690, K02DA021237, K08DA019951, U01DA020830, R01DA018673, R01DA012849, R01DA025888, R01DA012854)
- National Human Genome Research Institute (U01HG004738, U01HG004446, U01HG006513, U01HG004438, U01HG004436, HHSN268200782096C)
- National Cancer Institute (R01CA060691, N01 PC035145, N01 PC 35145, P01CA089392, U19CA148127, N01-PC35146, K07CA118412)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072488)
- National Institute of Neurological Disorders and Stroke (U01-NS069208, R01NS045012)
- National Institute of Dental and Craniofacial Research (R01DE012101, U01DE018903, R01DE014899)
- National Center for Research Resources (U54-RR020278, TL1RR024995, KL2RR024994, UL1RR024992)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R24HD041020)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- CHRNA5, rs16969968, smoking initiation age, early smoking onset, heavy smoking, cigarettes per day, genetic susceptibility to smoking, non-synonymous single nucleotide polymorphisms
- MeSH terms
- Adolescent, Adult, Europe, Female, Humans, Male, Nerve Tissue Proteins, Nicotine, Receptors, Nicotinic, Severity of Illness Index, Smoking, Tobacco Use Disorder, Age of Onset, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Adolescent Development, Genetic Association Studies, Gene-Environment Interaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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