ArticlePLoS medicine2017
Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach.
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Article in PLoS medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 208 papers, 18 of them syntheses that pooled it.
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208citing papers in PubMed, 18 pooled it
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Who cites it
208 citing papers in PubMed, 18 syntheses or guidelines pooled it, 388 citations in OpenAlex.
- Epigenome-wide association study of circulating interleukin-6 connects DNA methylation to immunometabolic and inflammatory health.Communications biology · 2026Pooled it
- Epigenome-wide association study meta-analysis of BMI in African Americans.HGG advances · 2026Pooled it
- Epigenetic timing effects on child developmental outcomes: a longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium.Genome medicine · 2025Pooled it
- Genome- and epigenome-wide association studies identify susceptibility of CpG sites and regions for metabolic syndrome in a Korean population.Clinical epigenetics · 2024Pooled it
- Identifying BMI-associated genes via a genome-wide multi-omics integrative approach using summary data.Human molecular genetics · 2024Pooled it
- DNA methylation analysis is used to identify novel genetic loci associated with circulating fibrinogen levels in blood.Journal of thrombosis and haemostasis : JTH · 2023Pooled it
- Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI.American journal of human genetics · 2023Pooled it
- Epigenome-wide association study of BMI in Black populations from InterGEN and GENOA.Obesity (Silver Spring, Md.) · 2023Pooled it
- Epigenome-wide association study of global cortical volumes in generation Scotland: Scottish family health study.Epigenetics · 2022Pooled it
- Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies.Breast cancer research : BCR · 2022Pooled it
- Pooled it
- Epigenome-wide association study of diet quality in the Women's Health Initiative and TwinsUK cohort.International journal of epidemiology · 2021Pooled it
- DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies.Genome medicine · 2020Pooled it
- Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease.Circulation · 2019Pooled it
- Mendelian Randomization and the Environmental Epigenetics of Health: a Systematic Review.Current environmental health reports · 2019Pooled it
- Meta-analysis of epigenome-wide association studies of cognitive abilities.Molecular psychiatry · 2018Pooled it
- Association of Methylation Signals With Incident Coronary Heart Disease in an Epigenome-Wide Assessment of Circulating Tumor Necrosis Factor α.JAMA cardiology · 2018Pooled it
- Sex differences in cardiovascular epigenetics-a systematic review.Biology of sex differences · 2018Pooled it
- Facial skin aging: an integrative analysis of genetics, epigenetics, and lifestyle factors.GeroScience · 2026Article
- Epigenetics and childhood obesity: DNA methylation coordinates environment and gene regulation.Endocrine reviews · 2026Review
148 more citing papers are in PubMed but not listed here.
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Authors and funding
49 authors at 20 institutions in 4 countries.
Michael M MendelsonFramingham Heart Study, Framingham, Massachusetts, United States of America.
Riccardo E MarioniCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
Roby JoehanesFramingham Heart Study, Framingham, Massachusetts, United States of America.
Chunyu LiuFramingham Heart Study, Framingham, Massachusetts, United States of America.
Åsa K HedmanMolecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0001-5413-204X
Stella AslibekyanDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Ellen W DemerathDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
Weihua GuanDivision of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
Degui ZhiDepartment of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Chen YaoFramingham Heart Study, Framingham, Massachusetts, United States of America.ORCID http://orcid.org/0000-0002-3944-7788
Tianxiao HuanFramingham Heart Study, Framingham, Massachusetts, United States of America.ORCID http://orcid.org/0000-0001-5840-9413
Christine WillingerFramingham Heart Study, Framingham, Massachusetts, United States of America.
Brian ChenPopulation Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America.ORCID http://orcid.org/0000-0001-9065-3301
Paul CourchesneFramingham Heart Study, Framingham, Massachusetts, United States of America.
Michael MulthaupCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Marguerite R IrvinDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Ariella CohainIcahn Institute for Genomics and Multiscale Biology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.ORCID http://orcid.org/0000-0003-2375-0683
Eric E SchadtIcahn Institute for Genomics and Multiscale Biology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Megan L GroveHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.ORCID http://orcid.org/0000-0001-6764-2508
Jan BresslerHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
Kari NorthDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Johan SundströmCardiovascular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Stefan GustafssonMolecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Sonia ShahQueensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Allan F McRaeQueensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Sarah E HarrisCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
Jude GibsonWellcome Trust Clinical Research Facility, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom.
Paul RedmondDepartment of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
Janie CorleyDepartment of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
Lee MurphyWellcome Trust Clinical Research Facility, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom.ORCID http://orcid.org/0000-0001-6467-7449
John M StarrCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
Erica KleinbrinkCenter for Molecular Medicine and Genetics and Department of Neurology, Wayne State University, Detroit, Michigan, United States of America.ORCID http://orcid.org/0000-0002-8565-207X
Leonard LipovichCenter for Molecular Medicine and Genetics and Department of Neurology, Wayne State University, Detroit, Michigan, United States of America.ORCID http://orcid.org/0000-0002-0531-3570
Peter M VisscherCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
Naomi R WrayQueensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Ronald M KraussChildren's Hospital Oakland Research Institute, Oakland, California, United States of America.
Daniele FallinCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.ORCID http://orcid.org/0000-0002-9948-3908
Andrew FeinbergCenter for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Devin M AbsherHudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States of America.ORCID http://orcid.org/0000-0003-4405-1646
Myriam FornageHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
James S PankowDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
Lars LindCardiovascular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Caroline FoxFramingham Heart Study, Framingham, Massachusetts, United States of America.
Erik IngelssonMolecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Donna K ArnettCollege of Public Health, University of Kentucky, Lexington, Kentucky, United States of America.
Eric BoerwinkleHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
Liming LiangDepartments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Daniel LevyFramingham Heart Study, Framingham, Massachusetts, United States of America.
Ian J DearyCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
National Institutes of Health · USThe University of Queensland · AUUppsala University · SEJohns Hopkins University · USUniversity of Alabama at Birmingham · USUniversity of Edinburgh · GBUniversity of Minnesota · USBoston University · USIcahn School of Medicine at Mount Sinai · USThe University of Texas Health Science Center at Houston · USWayne State University · USWestern General Hospital · GBAlzheimer Scotland · GBBaylor College of Medicine · USBrown Foundation · USHarvard University · USHudsonAlpha Institute for Biotechnology · USInstitute of Genetics and Cancer · GBUniversity of Kentucky · USUniversity of North Carolina at Chapel Hill · US
Funding
Framingham Project/LevyZIAHL006001 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEVY, DANIEL · 2009 to 2025
$51.1MTranslational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI DONALD K. SCOTT · 2015 to 2026
$27.7MBuilding on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6MTransgenic CoreP30DK046200 · NIDDK · TUFTS MEDICAL CENTER · PI GREENBERG, ANDREW S, PERISSI, VALENTINA · 1992 to 2021
$25.0MGenetic and Environmental Determinants of TriglyceridesU01HL072524 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI ARNETT, DONNA K · 2002 to 2008
$11.9MEpigenetic Determinants of Lipid Response to Dietary Fat and FenofibrateR01HL104135 · NHLBI · UNIVERSITY OF KENTUCKY · PI ARNETT, DONNA K · 2010 to 2015
$5.5MThe Role and Genetic Mechanism of Epigenetic Plasticity in Age-Related DiseaseR01AG042187 · NIA · JOHNS HOPKINS UNIVERSITY · PI FALLIN, M DANIELE, FEINBERG, ANDREW P. · 2011 to 2015
$4.1MLife, Death, and Function: The Primate-Specific Long Non-Coding RNA TranscriptomeDP2CA196375 · NCI · WAYNE STATE UNIVERSITY · PI LIPOVICH, LEONARD · 2014 to 2014
$2.3MCausal associations of circulating biomarkers with cardiovascular diseaseR01HL135313 · NHLBI · STANFORD UNIVERSITY · PI INGELSSON, ERIK · 2017 to 2019
$1.6MTHE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195N01HC025195 · HC · TRUSTEES OF BOSTON UNIVERSITY · PI WOLF, PHILIP A · 2002 to 2006
–Medical Research Council MR/K026992/1NCI NIH HHS DP2 CA196375NHLBI NIH HHS HHSN268201000010CNHLBI NIH HHS HHSN268201000011CNHLBI NIH HHS HHSN268201000012CNHLBI NIH HHS HHSN268201100001INHLBI NIH HHS HHSN268201100002INHLBI 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 HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS N01 HC025195NHLBI NIH HHS R01 HL104135NHLBI NIH HHS R01 HL135313NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS U01 HL072524NIA NIH HHS R01 AG042187NIDDK NIH HHS P30 DK020541NIDDK NIH HHS P30 DK046200Wellcome TrustWHI NIH HHS HHSN268201100001CWHI NIH HHS HHSN268201100002C
Abstract
backgroundThe link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. METHODS AND
findingsWe conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination.
conclusionsWe present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.
Indexed as
Body Mass IndexDNA MethylationGene Expression RegulationLipid MetabolismAgedCoronary Artery DiseaseEpigenesis, GeneticFemaleGenome-Wide Association StudyHumansLeukocytesMaleMendelian Randomization AnalysisObesityOligonucleotide Array Sequence Analysis
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