Evidence map›Paper›PMID 33593402›Full record

SynthesisClinical epigenetics2021

Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects.

C Christiansen, J E Castillo-Fernandez, A Domingo-Relloso, W Zhao, J S El-Sayed Moustafa, P-C Tsai, J Maddock, K Haack, S A Cole, S L R Kardia and 14 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 3 pooled it
6.4field-weighted citation impact, top 2% 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

55 citing papers in PubMed, 3 syntheses or guidelines pooled it, 88 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Smoking Cessation Interventions in Indigenous North Americans: A Meta-Narrative Systematic Review.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2023
    Pooled it
  4. Trial
  5. Review
  6. Article
  7. Article
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  10. Article
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  12. Article
  13. A blood- and brain-based EWAS of smoking.Nature communications · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Article
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  19. Review
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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

24 authors at 11 institutions in 4 countries.

C ChristiansenDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.ORCID 0000-0001-6034-5746
J E Castillo-FernandezDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
A Domingo-RellosoDepartment of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, USA.
W ZhaoDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
J S El-Sayed MoustafaDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
P-C TsaiDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
J MaddockMRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, UK.
K HaackPopulation Health Program, Texas Biomedical Research Institute, San Antonio, USA.
S A ColePopulation Health Program, Texas Biomedical Research Institute, San Antonio, USA.
S L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
M MolokhiaSchool of Population Health and Environmental Sciences, King's College London, London, UK.
M SudermanMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
C PowerPopulation, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, UK.
C ReltonMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
A WongMRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, UK.
D KuhMRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, UK.
A GoodmanCentre for Longitudinal Studies, UCL Social Research Institute, University College London, London, UK.
K S SmallDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
J A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
M Tellez-PlazaDepartment of Chronic Diseases Epidemiology, National Center for Epidemiology, Carlos III Health Institute, Madrid, Spain.
A Navas-AcienDepartment of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, USA.
G B PloubidisCentre for Longitudinal Studies, UCL Social Research Institute, University College London, London, UK.
R HardyMRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, UK.
J T BellDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK. jordana.bell@kcl.ac.uk.
King's College London · GBMRC Unit for Lifelong Health and Ageing · GBUniversity of Michigan · USGreat Ormond Street Hospital · GBTexas Biomedical Research Institute · USUniversity College London · GBChang Gung University · TWColumbia University · USInstituto de Salud Carlos III · ESUniversitat de València · ESUniversity of Bristol · GB

Funding

Training CoreP42ES010349 · NIEHS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI NAVAS-ACIEN, ANA · 2000 to 2020
$53.6M
True Metal fac coreP30ES009089 · NIEHS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MATTHEW S PERZANOWSKI · 1998 to 2026
$44.7M
The Strong Heart Study, Phase VU01HL041654 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI LEE, ELISA TAN · 1988 to 2013
$19.2M
STRONG HEART STUDY (SHS): OUHSC COORDINATING CENTER - TASK AREA B (B.1 AND B.3)75N92019D00027 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ZHANG, YING · 2019 to 2025
$15.5M
CARDIOVASCULAR DISEASE IN THE PIMA INDIANSU01HL041642 · NHLBI · MEDSTAR RESEARCH INSTITUTE · PI HOWARD, BARBARA V · 1988 to 2013
$12.6M
STRONG HEART FAMILY STUDYU01HL065520 · NHLBI · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI COLE, SHELLEY A · 2000 to 2011
$8.9M
CARDIOVASCULAR DISEASE IN SIOUX INDIANSU01HL041652 · NHLBI · U.S. PHS INDIAN HEALTH SERVICE · PI BEST, LYLE G · 1988 to 2013
$7.9M
STRONG HEART STUDY (SHS)-MISSOURI BREAKS INDUSTRIES RESEARCH, INC.- FIELD CENTER (FC) TASK AREA B (B.1 AND B.3)75N92019D00029 · NHLBI · MISSOURI BREAKS RESEARCH, INC. · PI FRETTS, AMANDA MAE · 2019 to 2025
$7.5M
STRONG HEART STUDY (SHS)- UNIVERSITY OF OKLAHOMA-FIELD CENTER (FC), TASK AREA B.3, YEAR 375N92019D00028 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ALI, TAUQEER · 2019 to 2025
$6.5M
STRONG HEART STUDY (SHS)- MEDSTAR HEALTH RESEARCH INSTITUTE (MHRI) FIELD CENTER -SUBTASK AREA B.2 PHASE VII EXAM AND EXAM CLOSEOUT.75N92019D00030 · NHLBI · MEDSTAR HEALTH RESEARCH INSTITUTE · PI UMANS, JASON G · 2019 to 2025
$5.2M
CVD in American Indians Study and Data Management Center and OK Field CenterR01HL109284 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI STONER, JULIE A · 2013 to 2018
$4.6M
CARDIOVASCULAR EVALUATION--STRONG HEART STUDY PHASE IVU01HL065521 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI DEVEREUX, RICHARD B · 2000 to 2013
$4.3M
Medical Research Council G0000934Medical Research Council G1001799Medical Research Council MC_UU_00011/5Medical Research Council MC_UU_00019/1Medical Research Council MC_UU_12019/2Medical Research Council MR/M004422/1Medical Research Council MR/N01104X/1NHLBI NIH HHS 75N92019D00027NHLBI NIH HHS 75N92019D00028NHLBI NIH HHS 75N92019D00029NHLBI NIH HHS 75N92019D00030NHLBI NIH HHS R01 HL090863NHLBI NIH HHS R01 HL109282NHLBI NIH HHS R01 HL109284NHLBI NIH HHS R01 HL109301NHLBI NIH HHS R01 HL109315NHLBI NIH HHS R01 HL109319NHLBI NIH HHS R01 HL119443NHLBI NIH HHS R01 HL133221NHLBI NIH HHS R01 HL141292NHLBI NIH HHS RC1 HL100185NHLBI NIH HHS U01 HL041642NHLBI NIH HHS U01 HL041652NHLBI NIH HHS U01 HL041654NHLBI NIH HHS U01 HL054457NHLBI NIH HHS U01 HL065520NHLBI NIH HHS U01 HL065521NIEHS NIH HHS P30 ES009089NIEHS NIH HHS P42 ES010349NIEHS NIH HHS R01 ES021367NIEHS NIH HHS R01 ES025216Wellcome TrustWellcome Trust 108439/Z/15/ZWellcome Trust MR/N01104X/1 2018-2020Wellcome Trust WT095219MA
6 · The paper itself

Abstract

backgroundSmoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers.

methodA smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989-1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA).

resultsAltogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results.

conclusionThis study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk.

Indexed as

AgedAmerican Indian or Alaska NativeBlack or African AmericanCase-Control StudiesCohort StudiesCpG IslandsDNA MethylationEnvironmental ExposureEpigenesis, GeneticEpigenomeFemaleGenome-Wide Association StudyHumansMaleMiddle AgedRisk FactorsSignaling Lymphocytic Activation Molecule FamilySLAMF7 protein, humanDNA methylationEnvironmentEpigeneticsLifestyleSLAMF7Smoking

Identifiers

PMID33593402
PMCPMC7888173
OpenAlexW3130601951

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Registered trials

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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.