Evidence map›Paper›PMID 31424985›Full record

SynthesisCirculation2019

Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease.

Golareh Agha, Michael M Mendelson, Cavin K Ward-Caviness, Roby Joehanes, TianXiao Huan, Rahul Gondalia, Elias Salfati, Jennifer A Brody, Giovanni Fiorito, Jan Bressler and 47 more

Open access · greenAbstract readMeta-Analysis
In one paragraph

Synthesis in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
140citing papers in PubMed, 3 pooled it
10.9field-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

140 citing papers in PubMed, 3 syntheses or guidelines pooled it, 273 citations in OpenAlex.

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80 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

57 authors at 1 institution in 1 country.

Golareh AghaDepartment of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York (G.A., A.A.B.).
Michael M MendelsonPopulation Sciences Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD (M.M.M., D.L., R.J.).
Cavin K Ward-CavinessNational Health and Environmental Effects Research Laboratory, Environmental Public Health Division, Chapel Hill, NC (C.K.W.C.).
Roby JoehanesPopulation Sciences Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD (M.M.M., D.L., R.J.).
TianXiao HuanThe Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD (T.X.H.).
Rahul GondaliaDepartment of Epidemiology (R.G.), University of North Carolina, Chapel Hill.
Elias SalfatiDepartment of Medicine, Stanford University School of Medicine, CA (E.S., P.S.T.).
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (J.A.B., J.S.F., K.L.W.).
Giovanni FioritoItalian Institute for Genomic Medicine (IIGM/HuGeF) and Department of Medical Sciences, University of Turin, Italy (G.F., S.G., G.M.).
Jan BresslerHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston (J.B.).
Brian H ChenTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD (B.H.C., T.T.).
Symen LigthartDepartment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands (S.L.).
Simonetta GuarreraItalian Institute for Genomic Medicine (IIGM/HuGeF) and Department of Medical Sciences, University of Turin, Italy (G.F., S.G., G.M.).
Elena ColicinoDepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY (E.C., A.C.J.).
Allan C JustDepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY (E.C., A.C.J.).
Simone WahlResearch Unit Molecualr Epidemiology, Helmholtz Zentrum München, Germany (S.W., C.G.).
Christian GiegerResearch Unit Molecualr Epidemiology, Helmholtz Zentrum München, Germany (S.W., C.G.).
Amy R VandiverCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD (A.R.V., M.M.).
Toshiko TanakaTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD (B.H.C., T.T.).
Dena G HernandezLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD (D.G.H., A.B.S.).
Luke C PillingEpidemiology and Public Health Group, University of Exeter Medical School, United Kingdom (L.C.P.).
Andrew B SingletonLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD (D.G.H., A.B.S.).
Carlotta SacerdoteUnit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy (C.S.).
Vittorio KroghEpidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy (V.K.).
Salvatore PanicoDipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy (S.P.).
Rosario TuminoCancer Registry And Histopathology Department, Civic- M.P. Arezzo2 Hospital, Asp Ragusa, Italy (R.T.).
Yun LiDepartment of Genetics, Department of Biostatistics, Department of Computer Science (Y.L.), University of North Carolina, Chapel Hill.
Guosheng ZhangCurriculum in Bioinformatics and Computational Biology, Department of Genetics, and Department of Statistics (G.Z.), University of North Carolina, Chapel Hill.
James D StewartCarolina Population Center and Department of Epidemiology (J.D.S.), University of North Carolina, Chapel Hill.
James S FloydCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (J.A.B., J.S.F., K.L.W.).
Kerri L WigginsCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (J.A.B., J.S.F., K.L.W.).
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA (J.I.R.).
Michael MulthaupCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD (A.R.V., M.M.).
Kelly BakulskiDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor (K.B.).
Steven HorvathDepartment of Human Genetics, David Geffen School of Medicine, University of California Los Angeles (S.H.).
Philip S TsaoDepartment of Medicine, Stanford University School of Medicine, CA (E.S., P.S.T.).
Devin M AbsherHudsonAlpha institute of Biotechnology, Huntsville, AL (D.M.A.).
Pantel VokonasVA Normative Aging Study, VA Boston Healthcare System, Department of Medicine, Boston University School of Medicine, MA (P.V.).
Joel HirschhornDepartment of Medicine, Division of Endocrinology, Boston Children's Hospital, MA (J.H.).
M Daniele FallinDepartment of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.D.F.).
Chunyu LiuDepartment of Biostatistics, Boston University School of Public Health, MA (C.L.).
Stefania BandinelliAzienda Sanitaria, USL Centro Firenze, Italy (S.B.).
Eric BoerwinkleHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston (E.B.).
Abbas DehghanDepartment of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of 346 Public Health, Imperial College London, United Kingdom (A.D.).
Joel D SchwartzDepartment of Epidemiology and Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA (J.D.S.).
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle (B.M.P.).
Andrew P FeinbergDepartments of Medicine, Biomedical Engineering, and Mental Health, Johns Hopkins University, Baltimore, MD (A.P.F.).
Lifang HouCenter for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center and Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL (L.H.).
Luigi FerrucciIntramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD (L.F.).
Nona SotoodehniaDivision of Cardiology, Departments of Medicine and Epidemiology, Cardiovascular Health Research Unit, University of Washington, Seattle (N.S.).
Giuseppe MatulloItalian Institute for Genomic Medicine (IIGM/HuGeF) and Department of Medical Sciences, University of Turin, Italy (G.F., S.G., G.M.).
Annette PetersHelmholtz Zentrum München, Institute of Epidemiology, Neuherberg, Germany; German Research Center for Cardiovascular Disease (DzHK e.V. - partner site Munich), Germany (A.P.).
Myriam FornageBrown Foundation Institute of Molecular Medicine McGovern Medical School, and Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston (M.F.).
Themistocles L AssimesDepartment of Medicine (Cardiovascular Medicine), and Department of Health Research & Policy, Stanford University School of Medicine, CA (T.L.A.).
Eric A WhitselDepartment of Epidemiology, Gillings School of Global Public Health, and Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill (E.A.W.).
Daniel LevyPopulation Sciences Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD (M.M.M., D.L., R.J.).
Andrea A BaccarelliDepartment of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York (G.A., A.A.B.).
University of Washington · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Harvard Clinical and Translational Science CenterUL1TR001102 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$106.2M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
True Metal fac coreP30ES009089 · NIEHS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MATTHEW S PERZANOWSKI · 1998 to 2026
$44.7M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
Building on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6M
South Texas Alzheimer's Disease Research CenterP30AG066546 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Claudia Kimie Suemoto · 2021 to 2026
$24.0M
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
Characterization of Normal Genomic VariabilityZIAAG000932 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW · 2009 to 2024
$11.3M
Exceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001102NCATS NIH HHS UL1 TR001881NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100001INHLBI NIH HHS HHSN268201100002INHLBI NIH HHS HHSN268201100003INHLBI NIH HHS HHSN268201100004INHLBI NIH HHS HHSN268201100046CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201300006CNHLBI NIH HHS HHSN268201700001CNHLBI NIH HHS HHSN268201700001INHLBI NIH HHS HHSN268201700002CNHLBI NIH HHS HHSN268201700002INHLBI NIH HHS HHSN268201700003CNHLBI NIH HHS HHSN268201700003INHLBI NIH HHS HHSN268201700004CNHLBI NIH HHS HHSN268201700004INHLBI NIH HHS HHSN268201700005INHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS K99 HL136875NHLBI NIH HHS N01 HC025195NHLBI 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 R01 HL087652NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL120393NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL130114NIA NIH HHS HHSN271201100004CNIA NIH HHS P30 AG066546NIA NIH HHS R01 AG023629NIA NIH HHS U01 AG052409NIDDK NIH HHS P30 DK063491NIEHS NIH HHS P30 ES009089NIEHS NIH HHS R01 ES014663NIEHS NIH HHS R01 ES015172NIEHS NIH HHS R01 ES020836NIEHS NIH HHS R01 ES021733NIEHS NIH HHS R01 ES025225NIEHS NIH HHS R01 ES027747NIEHS NIH HHS R21 ES020010NIMHD NIH HHS R01 MD009164NIMHD NIH HHS R01 MD013299NINDS NIH HHS R01 NS017950NINDS NIH HHS R01 NS087541WHI NIH HHS HHSN268201100001CWHI NIH HHS HHSN268201100002CWHI NIH HHS HHSN268201100003CWHI NIH HHS HHSN268201100004C
6 · The paper itself

Abstract

backgroundDNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.

methodsNine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts.

resultsAmong 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts.

conclusionMethylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD.

Indexed as

AdultAgedCohort StudiesCoronary DiseaseCpG IslandsDNA MethylationEuropeFemaleGenome-Wide Association StudyHumansIncidenceLeukocytesMaleMiddle AgedMyocardial InfarctionPopulation Groupscoronary artery diseasecoronary heart diseaseepigeneticsgene expression regulationgenomics

Identifiers

PMID31424985
PMCPMC6812683
OpenAlexW2969382515

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.