Evidence map›Paper›PMID 20700436›Full record

SynthesisPLoS genetics2010

Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.

Nancy L Saccone, Robert C Culverhouse, Tae-Hwi Schwantes-An, Dale S Cannon, Xiangning Chen, Sven Cichon, Ina Giegling, Shizhong Han, Younghun Han, Kaisu Keskitalo-Vuokko and 53 more

Open access · goldAbstract readComparative StudyMeta-Analysis
In one paragraph

Synthesis in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 255 papers, 22 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
255citing papers in PubMed, 22 pooled it
18.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

255 citing papers in PubMed, 22 syntheses or guidelines pooled it, 396 citations in OpenAlex.

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  11. Deep Sequencing of Three Loci Implicated in Large-Scale Genome-Wide Association Study Smoking Meta-Analyses.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2016
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195 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

63 authors at 20 institutions in 5 countries.

Nancy L SacconeDepartment of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA. nlims@genetics.wustl.edu
Robert C Culverhouse
Tae-Hwi Schwantes-An
Dale S Cannon
Xiangning Chen
Sven Cichon
Ina Giegling
Shizhong Han
Younghun Han
Kaisu Keskitalo-Vuokko
Xiangyang Kong
Maria Teresa Landi
Jennie Z Ma
Susan E Short
Sarah H Stephens
Victoria L Stevens
Lingwei Sun
Yufei Wang
Angela S Wenzlaff
Steven H Aggen
Naomi Breslau
Peter Broderick
Nilanjan Chatterjee
Jingchun Chen
Andrew C Heath
Markku Heliövaara
Nicole R Hoft
David J Hunter
Majken K Jensen
Nicholas G Martin
Grant W Montgomery
Tianhua Niu
Thomas J Payne
Leena Peltonen
Michele L Pergadia
John P Rice
Richard Sherva
Margaret R Spitz
Juzhong Sun
Jen C Wang
Robert B Weiss
William Wheeler
Stephanie H Witt
Bao-Zhu Yang
Neil E Caporaso
Marissa A Ehringer
Tim Eisen
Susan M Gapstur
Joel Gelernter
Richard Houlston
Jaakko Kaprio
Kenneth S Kendler
Peter Kraft
Mark F Leppert
Ming D Li
Pamela A F Madden
Markus M Nöthen
Sreekumar Pillai
Marcella Rietschel
Dan Rujescu
Ann Schwartz
Christopher I Amos
Laura J Bierut
Washington University in St. Louis · USVirginia Commonwealth University · USAmerican Cancer Society · USHarvard University · USInstitute of Cancer Research · GBThe University of Texas MD Anderson Cancer Center · USUniversity of Colorado Boulder · USUniversity of Utah · USUniversity of Virginia · USYale University · USCentral Institute of Mental Health · DEDivision of Cancer Epidemiology and GeneticsFinnish Institute for Health and Welfare · FIGlaxoSmithKline (United States) · USLudwig-Maximilians-Universität München · DEMichigan United · USQIMR Berghofer Medical Research Institute · AUUniversity of Helsinki · FIBoston University · USBrown University · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Wave IV Data CollectionP01HD031921 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HARRIS, KATHLEEN MULLAN · 1994 to 2020
$86.1M
Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, TAMIMI, RULLA M · 2000 to 2019
$77.8M
Tumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI PAUL M STEMMER · 1985 to 2026
$68.4M
JH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2M
Twin StudyP60DA011015 · NIDA · UNIVERSITY OF COLORADO DENVER · PI HEWITT, JOHN K. · 1997 to 2013
$22.5M
A Center for GEI Association StudiesU01HG004424 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY · 2007 to 2010
$21.4M
The Collaborative Genetic Study of Nicotine DependenceP01CA089392 · NCI · WASHINGTON UNIVERSITY · PI BIERUT, LAURA J. · 2001 to 2012
$17.3M
Pilot Project ProgramP30ES007784 · NIEHS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI JOHNSON, DAVID G. · 1996 to 2011
$16.4M
Surveillance, Epidemiology and End Results (SEER) Program - Wayne StateN01PC35145 · NCI · WAYNE STATE UNIVERSITY · PI SCHWARTZ, ANN · 2007 to 2009
$14.6M
Dietary Etiology of Heart DiseaseR01HL035464 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI ERIC B RIMM, Qi Sun · 1986 to 2026
$13.6M
PILOT--GENETIC EPIDEMIOLOGY OF ALCOHOL AND TOBACCO CONSUMPTION IN CHINESE SAMPLEP50AA011998 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 1999 to 2008
$12.6M
Intramural NIH HHSNCI NIH HHS CA016672NCI NIH HHS CA121197NCI NIH HHS CA127219NCI NIH HHS CA133996NCI NIH HHS CA55769NCI NIH HHS N01 CN025404NCI NIH HHS N01 CN025476NCI NIH HHS N01 CN025511NCI NIH HHS N01 CN025512NCI NIH HHS N01 CN025513NCI NIH HHS N01 CN025514NCI NIH HHS N01 CN025515NCI NIH HHS N01 CN025516NCI NIH HHS N01 CN025518NCI NIH HHS N01 CN025522NCI NIH HHS N01 CN025524NCI NIH HHS N01 CN075022NCI NIH HHS N01-CN-25404NCI NIH HHS N01-CN-25476NCI NIH HHS N01-CN-25511NCI NIH HHS N01-CN-25512NCI NIH HHS N01-CN-25513NCI NIH HHS N01-CN-25514NCI NIH HHS N01-CN-25515NCI NIH HHS N01-CN-25516NCI NIH HHS N01-CN-25518NCI NIH HHS N01-CN-25522NCI NIH HHS N01 CN-25524NCI NIH HHS N01 CN-75022NCI NIH HHS N01 PC035145NCI NIH HHS N01 PC35145NCI NIH HHS P01 CA087969NCI NIH HHS P01CA087969NCI NIH HHS P01 CA089392NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA022453NCI NIH HHS P30 CA22453NCI NIH HHS R01 CA055769NCI NIH HHS R01 CA060691NCI NIH HHS R01 CA087895NCI NIH HHS R01 CA121197NCI NIH HHS R01 CA127219NCI NIH HHS R01 CA133996NCI NIH HHS R01 CA60691NCI NIH HHS R01 CA87895NHGRI NIH HHS 5U01HG004399NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01 HG004399NHGRI NIH HHS U01 HG004422NHGRI NIH HHS U01 HG004424NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01HG004438NHGRI NIH HHS U01 HG004446NHGRI NIH HHS U01 HG04422-01NHGRI NIH HHS U01HG04424NHLBI NIH HHS 5R01HL035464NHLBI NIH HHS P01 HL072903NHLBI NIH HHS P01-HL72903NHLBI NIH HHS R01 HL035464NIAAA NIH HHS AA11330NIAAA NIH HHS K01 AA015336NIAAA NIH HHS K05 AA017688NIAAA NIH HHS P50 AA011998NIAAA NIH HHS R01 AA011330NIAAA NIH HHS R01 AA011949NIAAA NIH HHS R01 AA013320NIAAA NIH HHS R01 AA013321NIAAA NIH HHS R01 AA017889NIAAA NIH HHS R01 AA11998NIAAA NIH HHS R01 AA13320NIAAA NIH HHS R01 AA13321NIAAA NIH HHS T32 AA007464NICHD NIH HHS P01 HD031921NICHD NIH HHS P01 HD31921NICHD NIH HHS R24 HD041020NIDA NIH HHS DA12849NIDA NIH HHS DA-13783NIDA NIH HHS K01 DA019498NIDA NIH HHS K01DA019498NIDA NIH HHS K01 DA024758NIDA NIH HHS K01DA024758NIDA NIH HHS K02 DA021237NIDA NIH HHS K08 DA019951NIDA NIH HHS P60 DA011015NIDA NIH HHS R01 DA012844NIDA NIH HHS R01 DA012845NIDA NIH HHS R01 DA012849NIDA NIH HHS R01 DA012854NIDA NIH HHS R01 DA013783NIDA NIH HHS R01 DA021913NIDA NIH HHS R01 DA026911NIDA NIH HHS R01 DA-12844NIDA NIH HHS R01 DA12854NIDA NIH HHS R01 DA12890NIDA NIH HHS R03 DA023166NIDA NIH HHS R21 DA026901NIDA NIH HHS R21 DA027070NIDA NIH HHS R21DA027070NIDA NIH HHS R56 DA012854NIDA NIH HHS R56 DA12854NIDDK NIH HHS 5P01DK070756NIDDK NIH HHS P01 DK070756NIEHS NIH HHS P30 ES007784NIEHS NIH HHS P30ES007784NIEHS NIH HHS R25 ES011080NIGMS NIH HHS K25 GM069590NIGMS NIH HHS K25 GM69590Wellcome Trust
6 · The paper itself

Abstract

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10(-35) and <10(-8) respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10(-6)). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10(-20)) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue.

Indexed as

AdolescentAdultAgedAged, 80 and overChromosomes, Human, Pair 15FemaleHumansLung NeoplasmsMaleMiddle AgedNerve Tissue ProteinsPolymorphism, Single NucleotidePulmonary Disease, Chronic ObstructiveReceptors, NicotinicSmokingWhite PeopleCHRNA5 protein, humanNerve Tissue ProteinsReceptors, Nicotinic

Identifiers

PMID20700436
PMCPMC2916847
OpenAlexW2108344795

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.