SynthesisMolecular psychiatry2016
Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.
Open access · greenAbstract readComparative StudyMeta-Analysis
In one paragraph
Synthesis in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 2 pooled it
3.6field-weighted citation impact, top 7% 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Loci on chromosome 20 interact with rs16969968 to influence cigarettes per day in European ancestry individuals.Drug and alcohol dependence · 2024Pooled it
- Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use.Biological psychiatry · 2019Pooled it
- Disruption ofiScience · 2026Article
- Boosting the Power of Rare Variant Association Studies by Imputation Using Large-scale Sequencing Population.Genomics, proteomics & bioinformatics · 2025Article
- The genetic landscape of substance use disorders.Molecular psychiatry · 2024Review
- Article
- Transcriptional changes in the rat brain induced by repetitive transcranial magnetic stimulation.Frontiers in human neuroscience · 2023Article
- 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
- Nicotinic acetylcholine receptors and nicotine addiction: A brief introduction.Neuropharmacology · 2020Review
- 2018 Langley Award for Basic Research on Nicotine and Tobacco: Bringing Precision Medicine to Smoking Cessation.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2020Review
- Common and Rare Variants Genetic Association Analysis of Cigarettes per Day Among Ever-Smokers in Chronic Obstructive Pulmonary Disease Cases and Controls.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019Article
- Impact of single nucleotide polymorphisms on P450 oxidoreductase and peroxisome proliferator-activated receptor alpha on tacrolimus pharmacokinetics in renal transplant recipients.The pharmacogenomics journal · 2019Article
- CHRNA5 and CHRNA3 polymorphism and lung cancer susceptibility in Palestinian population.BMC research notes · 2018Article
- The Value of Biosamples in Smoking Cessation Trials: A Review of Genetic, Metabolomic, and Epigenetic Findings.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2018Review
- Human Genetics of Addiction: New Insights and Future Directions.Current psychiatry reports · 2018Review
- Toward the implementation of genomic applications for smoking cessation and smoking-related diseases.Translational behavioral medicine · 2018Review
- Genome-wide meta-analysis identifies a novel susceptibility signal at CACNA2D3 for nicotine dependence.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2017Article
- Deep Sequencing of 71 Candidate Genes to Characterize Variation Associated with Alcohol Dependence.Alcoholism, clinical and experimental research · 2017Article
- Targeted sequencing identifies genetic polymorphisms of flavin-containing monooxygenase genes contributing to susceptibility of nicotine dependence in European American and African American.Brain and behavior · 2017Article
- Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population.Lung cancer (Amsterdam, Netherlands) · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
53 authors at 20 institutions in 2 countries.
E OlfsonDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
N L SacconeDepartment of Genetics, Washington University School of Medicine, St Louis, MO, USA.
E O JohnsonBehavioral Health Epidemiology program, RTI International, Research Triangle Park, NC, USA.
L-S ChenDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
R CulverhouseDepartment of Medicine and Division of Biostatistics, Washington University School of Medicine, St Louis, MO, USA.
K DohenyCenter for Inherited Disease Research, Johns Hopkins University, Baltimore, MD, USA.
S M FoltzDepartment of Genetics, Washington University School of Medicine, St Louis, MO, USA.
L FoxDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
S M GogartenDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
S HartzDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
K HetrickCenter for Inherited Disease Research, Johns Hopkins University, Baltimore, MD, USA.
C C LaurieDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
B MarosyCenter for Inherited Disease Research, Johns Hopkins University, Baltimore, MD, USA.
N AminDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
D ArnettDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
R G BarrDepartments of Medicine and Epidemiology, Columbia University Medical Center, New York, NY, USA.
T M BartzCardiovascular Health Research Unit, Departments of Medicine and Biostatistics, University of Washington, Seattle, WA, USA.
S BertelsenDepartment of Neurosciences, Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
I B BoreckiDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.
M R BrownHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
D I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
C M van DuijnDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
M F FeitosaDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.
E R FoxUniversity of Mississippi Medical Center, Jackson, MS, USA.
N FranceschiniDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
O H FrancoDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
M L GroveHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
X GuoInstitute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
A HofmanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
S L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
A C MorrisonHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
S K MusaniUniversity of Mississippi Medical Center, Jackson, MS, USA.
B M PsatyCardiovascular Health Research Unit, Departments of Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA, USA.
D C RaoDivision of Biostatistics, Washington University School of Medicine in St. Louis, St Louis, MO, USA.
A P ReinerFred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA, USA.
K RiceDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
P M RidkerDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
L M RoseDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
U M SchickFred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA, USA.
K SchwanderDivision of Biostatistics, Washington University School of Medicine in St. Louis, St Louis, MO, USA.
A G UitterlindenDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
D VojinovicDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
J-C WangDepartment of Neurosciences, Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
E B WareDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
G WilsonJackson State University, School of Public Service, Jackson, MS, USA.
J YaoInstitute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
W ZhaoDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
N BreslauDepartment of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA.
D HatsukamiDepartment of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
J A StitzelInstitute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.
J RiceDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
A GoateDepartment of Neurosciences, Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
L J BierutDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Washington University in St. Louis · USErasmus MC · NLUniversity of Washington · USIcahn School of Medicine at Mount Sinai · USJohns Hopkins University · USThe University of Texas Health Science Center at Houston · USUniversity of Michigan–Ann Arbor · USBrigham and Women's Hospital · USFred Hutch Cancer Center · USJackson Memorial Hospital · USColumbia University Irving Medical Center · USHarbor–UCLA Medical Center · USHarvard University · USJackson State University · USKaiser Permanente Washington Health Research Institute · USMichigan State University · USRTI International · USThe Lundquist Institute · USUniversity of Alabama at Birmingham · USUniversity of Colorado Boulder · US
Funding
Subject CollectionU10AA008401 · NIAAA · SUNY DOWNSTATE MEDICAL CENTER · PI JAY Arnold TISCHFIELD · 1989 to 2026
$162.7MInstitute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8MNATIONAL RESEARCH SERVICE AWARD-MEDICAL SCIENTISTT32GM007200 · NIGMS · WASHINGTON UNIVERSITY · PI YOKOYAMA, WAYNE M. · 1985 to 2024
$59.8MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MWashington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILES Frome WILKINSON · 2003 to 2026
$40.4MWomen's Health Study: Continued Follow-upR01CA047988 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 1991 to 2014
$28.2MBuilding on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MGenome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2MPulmonary microvascular perfusion in the Multi-Ethnic Study of AtherosclerosisR01HL077612 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI R Graham BARR · 2004 to 2026
$18.8MHYPERGEN: GENETICS OF LEFT VENTRICULAR HYPERTROPHYR01HL055673 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI ARNETT, DONNA K · 1996 to 2016
$18.1MNCATS NIH HHS TL1 TR000449NCATS NIH HHS TL1TR000449NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1TR000040NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCATS NIH HHS UL1 TR000448NCATS NIH HHS UL1TR000448NCI NIH HHS CA047988NCI NIH HHS P01 CA089392NCI NIH HHS P01CA89392NCI NIH HHS R01 CA047988NCI NIH HHS U19 CA148127NCI NIH HHS U19CA148172NCI NIH HHS UM1 CA182913NCRR NIH HHS UL1 RR025005NCRR NIH HHS UL1RR025005NHLBI NIH HHS 5RC2HL102419NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100001INHLBI NIH HHS HHSN268201100002INHLBI NIH HHS HHSN268201100003INHLBI NIH HHS HHSN268201100004INHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201100046CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201300046CNHLBI NIH HHS HHSN268201300047CNHLBI NIH HHS HHSN268201300048CNHLBI NIH HHS HHSN268201300049CNHLBI NIH HHS HHSN268201300050CNHLBI NIH HHS HL054457NHLBI NIH HHS HL054464NHLBI NIH HHS HL054481NHLBI NIH HHS HL071917NHLBI NIH HHS HL080467NHLBI NIH HHS HL103010NHLBI NIH HHS HL118305NHLBI NIH HHS HL119443NHLBI NIH HHS HL54471NHLBI NIH HHS HL54472NHLBI NIH HHS HL54473NHLBI NIH HHS HL54495NHLBI NIH HHS HL54496NHLBI NIH HHS HL54497NHLBI NIH HHS HL54509NHLBI NIH HHS HL54515NHLBI NIH HHS HL87660NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N02 HL064278NHLBI NIH HHS R01 HL043851NHLBI NIH HHS R01 HL055673NHLBI NIH HHS R01HL055673NHLBI NIH HHS R01 HL068986NHLBI NIH HHS R01HL068986NHLBI NIH HHS R01 HL071051NHLBI NIH HHS R01HL071051NHLBI NIH HHS R01 HL071205NHLBI NIH HHS R01HL071205NHLBI NIH HHS R01 HL071250NHLBI NIH HHS R01HL071250NHLBI NIH HHS R01 HL071251NHLBI NIH HHS R01HL071251NHLBI NIH HHS R01 HL071252NHLBI NIH HHS R01HL071252NHLBI NIH HHS R01 HL071258NHLBI NIH HHS R01HL071258NHLBI NIH HHS R01 HL071259NHLBI NIH HHS R01HL071259NHLBI NIH HHS R01 HL071917NHLBI NIH HHS R01 HL077612NHLBI NIH HHS R01 HL080467NHLBI NIH HHS R01 HL085251NHLBI NIH HHS R01HL085251NHLBI NIH HHS R01HL086694NHLBI NIH HHS R01HL087641NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01HL087652NHLBI NIH HHS R01 HL087660NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01HL105756NHLBI NIH HHS R01 HL117078NHLBI NIH HHS R01 HL118305NHLBI NIH HHS R01HL118305NHLBI NIH HHS R01 HL119443NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01HL120393NHLBI NIH HHS R01HL55673NHLBI NIH HHS R01HL59367NHLBI NIH HHS R21 HL123677NHLBI NIH HHS R21HL123677NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS RC2 HL103010NHLBI NIH HHS U01 HL054457NHLBI NIH HHS U01 HL054464NHLBI NIH HHS U01 HL054471NHLBI NIH HHS U01 HL054472NHLBI NIH HHS U01 HL054473NHLBI NIH HHS U01 HL054481NHLBI NIH HHS U01 HL054495NHLBI NIH HHS U01 HL054496NHLBI NIH HHS U01 HL054497NHLBI NIH HHS U01 HL054509NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01HL080295NHLBI NIH HHS U01HL54473NHLBI NIH HHS U10 HL054457NHLBI NIH HHS U10 HL054464NHLBI NIH HHS U10 HL054471NHLBI NIH HHS U10 HL054472NHLBI NIH HHS U10 HL054473NHLBI NIH HHS U10 HL054481NHLBI NIH HHS U10 HL054495NHLBI NIH HHS U10 HL054496NHLBI NIH HHS U10 HL054497NHLBI NIH HHS U10 HL054509NHLBI NIH HHS UC2 HL103010NIAAA NIH HHS F30 AA023685NIAAA NIH HHS F30AA023685NIAAA NIH HHS U10 AA008401NIAAA NIH HHS U10AA008401NIA NIH HHS HHSN271201100004CNIA NIH HHS R01 AG023629NIA NIH HHS R01AG023629NIA NIH HHS R01 AG055406NIDA NIH HHS K08 DA030398NIDA NIH HHS K08 DA032680NIDA NIH HHS R01 DA025888NIDA NIH HHS R01DA025888NIDA NIH HHS R01 DA026911NIDA NIH HHS R01 DA038076NIDDK NIH HHS DK063491NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK089256NIDDK NIH HHS R01DK089256NIGMS NIH HHS T32 GM007200NIGMS NIH HHS T32GM07200NINDS NIH HHS NS041558NINDS NIH HHS R01 NS041558WHI NIH HHS HHSN268201100001CWHI NIH HHS HHSN268201100002CWHI NIH HHS HHSN268201100003CWHI NIH HHS HHSN268201100004C
Abstract
The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine-dependent cases (Fagerström Test for Nicotine Dependence score⩾4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (minor allele frequency (MAF)⩾0.05), aggregate low frequency variants (0.05>MAF⩾0.005) and aggregate rare variants (MAF<0.005). Meta-analysis of primary results was performed with replication studies containing 12 174 heavy and 11 290 light smokers. Next-generation sequencing with 180 × coverage identified 24 nonsynonymous variants and 2 frameshift deletions in CHRNA5, including 9 novel variants in the 2820 subjects. Meta-analysis confirmed the risk effect of the only common variant (rs16969968, European ancestry: odds ratio (OR)=1.3, P=3.5 × 10(-11); African ancestry: OR=1.3, P=0.01) and demonstrated that three low frequency variants contributed an independent risk (aggregate term, European ancestry: OR=1.3, P=0.005; African ancestry: OR=1.4, P=0.0006). The remaining 22 rare coding variants were associated with increased risk of nicotine dependence in the European American primary sample (OR=12.9, P=0.01) and in the same risk direction in African Americans (OR=1.5, P=0.37). Our results indicate that common, low frequency and rare CHRNA5 coding variants are independently associated with nicotine dependence risk. These newly identified variants likely influence the risk for smoking-related diseases such as lung cancer.
Indexed as
Genetic Predisposition to DiseaseAdultBlack or African AmericanFemaleGenetic VariationHumansMaleMiddle AgedNerve Tissue ProteinsReceptors, NicotinicTobacco Use DisorderWhite PeopleCHRNA5 protein, humanNerve Tissue ProteinsReceptors, Nicotinic
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