SynthesisArchives of general psychiatry2012
Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.
Open access · greenAbstract readMeta-Analysis
In one paragraph
Synthesis in Archives of general psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 5 pooled it
6.7field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 5 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Dynamic change in the association of a cigarettes-per-day polygenic risk score across the numeric range of its corresponding phenotype over adolescence and young adulthood.Addictive behaviors · 2021Pooled it
- Genotype × Environment Interaction in Smoking Behaviors: A Systematic Review.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2017Pooled it
- Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.Behavior genetics · 2016Pooled it
- CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis.Journal of the National Cancer Institute · 2015Pooled it
- Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.Genetic epidemiology · 2013Pooled it
- Nicotinic acetylcholine receptor variation and response to smoking cessation therapies.Pharmacogenetics and genomics · 2013Trial
- Initial Drug Sensitivity and Vulnerability to Substance Use Disorders: A Review of Individual Influences.Biology · 2026Review
- Maternal Smoking During Pregnancy Interacts With Genetic Factors to Increase Risk for Low Birth Weight but Not Harmful Offspring Smoking Behaviors in Europeans.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2025Article
- The relationship between cannabis and cardiovascular disease: clearing the haze.Nature reviews. Cardiology · 2025Review
- Challenges in studying the interplay of genes and environment. A study of childhood financial distress moderating genetic predisposition for peak smoking.Journal Of Economic Psychology · 2023Article
- Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes.Translational psychiatry · 2022Article
- Mutation of the α5 nicotinic acetylcholine receptor subunit increases ethanol and nicotine consumption in adolescence and impacts adult drug consumption.Neuropharmacology · 2022Article
- A systematic analysis of protein-altering exonic variants in chronic obstructive pulmonary disease.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Little Evidence of Modified Genetic Effect of rs16969968 on Heavy Smoking Based on Age of Onset of Smoking.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2021Article
- Genetics of Smoking Behaviors in American Indians.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Article
- The Influence of Recreational Substance Use in TMS Research.Brain sciences · 2020Review
- A trans-ethnic two-stage polygenetic scoring analysis detects genetic correlation between osteoporosis and schizophrenia.Clinical and translational medicine · 2020Article
- Testing Familial Transmission of Smoking With Two Different Research Designs.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2018Article
- Post-GWAS in Psychiatric Genetics: A Developmental Perspective on the "Other" Next Steps.Genes, brain, and behavior · 2018Review
- Early maturation and substance use across adolescence and young adulthood: A longitudinal study of Finnish twins.Development and psychopathology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
152 authors at 20 institutions in 10 countries.
Sarah M HartzWashington University School of Medicine, St Louis, Missouri, USA.
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
Washington University in St. Louis · USNational Institutes of Health · USThe University of Texas MD Anderson Cancer Center · USUniversity of Helsinki · FIJohns Hopkins University · USVrije Universiteit Amsterdam · NLLudwig-Maximilians-Universität München · DEVirginia Commonwealth University · USdeCODE Genetics (Iceland) · ISFinnish Institute for Health and Welfare · FIUniversity of Colorado Boulder · USUniversity of Maryland, Baltimore · USUniversity of Utah · USYale University · USQIMR Berghofer Medical Research Institute · AUSRI International · USStatens Serum Institut · DKUniversity of Chicago · USUniversity of North Carolina at Chapel Hill · USAmerican Cancer Society · US
Funding
Subject CollectionU10AA008401 · NIAAA · SUNY DOWNSTATE MEDICAL CENTER · PI JESSICA E SALVATORE · 1989 to 2026
$162.7MWashington University Institute of Clinical and Translational Sciences (UL1)UL1RR024992 · NCRR · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2007 to 2011
$45.4MWashington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4MPsychosocial Influences on Rural Children's Oral HealthR01DE014899 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FOXMAN, BETSY, MARAZITA, MARY L. · 2002 to 2020
$39.9MJH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2MUniversity of Toronto Coordinating Genetics Core & Clinical Trial SiteU01DA020830 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI CINCIRIPINI, PAUL MICHAEL · 2005 to 2014
$22.4MResearch BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3MThe Collaborative Genetic Study of Nicotine DependenceP01CA089392 · NCI · WASHINGTON UNIVERSITY · PI RICE, JOHN P · 2001 to 2012
$17.3MAN NCRR CENTER FOR HIGH THROUGHPUT SNP GENOTYPING AND ANALYSIS: GAIN NETWORKU54RR020278 · NCRR · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY · 2004 to 2008
$14.4MSex-specific analysis of opioid dependence GWAS and beyondR01DA012690 · NIDA · YALE UNIVERSITY · PI GELERNTER, JOEL · 2000 to 2017
$14.0MFluoride & Other Factors in Childhood and Adolescent Bone DevelopmentR01DE012101 · NIDCR · UNIVERSITY OF IOWA · PI LEVY, STEVEN M. · 1998 to 2013
$11.9MGENETICS OF COCAINE DEPENDENCER01DA012849 · NIDA · YALE UNIVERSITY · PI GELERNTER, JOEL · 1999 to 2010
$11.5MFDA HHS R01 FD003706Intramural NIH HHS Z99 AG999999Intramural NIH HHS ZIA AG000196Medical Research Council MC_PC_U127561128NCATS NIH HHS KL2 TR000450NCATS NIH HHS TL1 TR000449NCATS NIH HHS UL1 TR000448NCI NIH HHS K07 CA118412NCI NIH HHS N01 PC035145NCI NIH HHS N01-PC35145NCI NIH HHS N01-PC35146NCI NIH HHS P01 CA089392NCI NIH HHS R01 CA060691NCI NIH HHS R01CA060691NCI NIH HHS U19 CA148127NCRR NIH HHS KL2 RR024994NCRR NIH HHS TL1 RR024995NCRR NIH HHS U54 RR020278NCRR NIH HHS UL1 RR024992NCRR NIH HHS UL1RR024992NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01 HG004436NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01HG004438NHGRI NIH HHS U01 HG004446NHGRI NIH HHS U01HG004446NHGRI NIH HHS U01 HG004738NHGRI NIH HHS U01HG004738NHGRI NIH HHS U01 HG006513NHLBI NIH HHS N01 HR046002NHLBI NIH HHS R01 HL089651NHLBI NIH HHS R01HL089651-01NIAAA NIH HHS K02 AA018755NIAAA NIH HHS K05 AA017688NIAAA NIH HHS R01 AA011330NIAAA NIH HHS R01 AA017535NIAAA NIH HHS R01 AA11330NIAAA NIH HHS U10 AA008401NIA NIH HHS N01 AG012100NIA NIH HHS N01-AG-1-2109NIA NIH HHS R03 AG035146NICHD NIH HHS R24 HD041020NIDA NIH HHS DA019951NIDA NIH HHS DA12854NIDA NIH HHS K01 DA019498NIDA NIH HHS K01 DA024758NIDA NIH HHS K01DA19498NIDA NIH HHS K01DA24758NIDA NIH HHS K02 DA021237NIDA NIH HHS K02DA021237NIDA NIH HHS K08 DA019951NIDA NIH HHS K08 DA030398NIDA NIH HHS K08 DA032680NIDA NIH HHS R01 DA003706NIDA NIH HHS R01 DA012690NIDA NIH HHS R01 DA012849NIDA NIH HHS R01 DA012854NIDA NIH HHS R01 DA017932NIDA NIH HHS R01 DA018673NIDA NIH HHS R01 DA025888NIDA NIH HHS R01 DA026911NIDA NIH HHS R01DA026911NIDA NIH HHS R01 DA03706NIDA NIH HHS R01 DA12690NIDA NIH HHS R01 DA12849NIDA NIH HHS R01DA25888NIDA NIH HHS R21 DA027070NIDA NIH HHS R21DA027070NIDA NIH HHS R21 DA033827NIDA NIH HHS R21DA033827NIDA NIH HHS R56 DA012854NIDA NIH HHS U01 DA020830NIDA NIH HHS U01DA02830NIDCR NIH HHS R01 DE012101NIDCR NIH HHS R01 DE014899NIDCR NIH HHS U01 DE018903NIDCR NIH HHS U01-DE018903NIDDK NIH HHS P30 DK072488NIMH NIH HHS MH46289NIMH NIH HHS MH46318NIMH NIH HHS R01 MH059565NIMH NIH HHS R01 MH059566NIMH NIH HHS R01 MH059571NIMH NIH HHS R01 MH059586NIMH NIH HHS R01 MH059587NIMH NIH HHS R01 MH059588NIMH NIH HHS R01 MH060870NIMH NIH HHS R01 MH060879NIMH NIH HHS R01 MH061675NIMH NIH HHS R01 MH067257NIMH NIH HHS R01 MH081800NIMH NIH HHS R01 MH59565NIMH NIH HHS R01 MH59566NIMH NIH HHS R01 MH59571NIMH NIH HHS R01 MH59586NIMH NIH HHS R01 MH59587NIMH NIH HHS R01 MH59588NIMH NIH HHS R01 MH60870NIMH NIH HHS R01 MH60879NIMH NIH HHS R01 MH61675NIMH NIH HHS R01 MH67257NIMH NIH HHS R01 MH81800NIMH NIH HHS T32 MH014677NIMH NIH HHS U01 MH046276NIMH NIH HHS U01 MH046289NIMH NIH HHS U01 MH046318NIMH NIH HHS U01 MH079469NIMH NIH HHS U01 MH079470NIMH NIH HHS U01 MH79469NIMH NIH HHS U01 MH79470NINDS NIH HHS R01 NS045012NINDS NIH HHS R01NS45012NINDS NIH HHS U01 NS069208Wellcome Trust 090532
Abstract
contextRecent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968.
objectiveTo 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).
conclusionThese results highlight an increased genetic vulnerability to smoking in early-onset smokers.
Indexed as
SmokingTobacco Use DisorderAdolescentAdolescent DevelopmentAdultAge of OnsetEuropeFemaleGene-Environment InteractionGenetic Association StudiesGenetic Predisposition to DiseaseHumansMaleNerve Tissue ProteinsNicotinePolymorphism, Single NucleotideCHRNA5 protein, humanNerve Tissue ProteinsNicotineReceptors, Nicotinic
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