Evidence map›Paper›PMID 27717399›Full record

ArticleGenome biology2016

An epigenetic clock for gestational age at birth based on blood methylation data.

Anna K Knight, Jeffrey M Craig, Christiane Theda, Marie Bækvad-Hansen, Jonas Bybjerg-Grauholm, Christine S Hansen, Mads V Hollegaard, David M Hougaard, Preben B Mortensen, Shantel M Weinsheimer and 37 more

Abstract read
In one paragraph

Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
167citing papers in PubMed, 6 pooled it
–field-weighted citation impact
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

167 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. Pooled it
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  10. Article
  11. Promotion of long-term health in early life.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  12. Article
  13. DNA methylation as proxy of genetic, prenatal and perinatal psychiatric risk factors.medRxiv : the preprint server for health sciences · 2026
    Article
  14. Review
  15. Article
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107 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

47 authors.

Anna K KnightGenetics and Molecular Biology Program, Emory University, Atlanta, GA, USA.
Jeffrey M CraigMurdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia.
Christiane ThedaThe Royal Women's Hospital, Murdoch Childrens Research Institute and University of Melbourne, Parkville, Victoria, 3052, Australia.
Marie Bækvad-HansenSection of Neonatal Genetics, Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark.
Jonas Bybjerg-GrauholmSection of Neonatal Genetics, Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark.
Christine S HansenSection of Neonatal Genetics, Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark.
Mads V HollegaardSection of Neonatal Genetics, Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark.
David M HougaardSection of Neonatal Genetics, Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark.
Preben B MortensenNational Centre for Register-based Research, School of Business and Social Sciences, Aarhus University, Fuglesangs Allé 4, 8210, Aarhus V, Denmark.
Shantel M WeinsheimerInstitute of Biological Psychiatry, Sct. Hans Mental Health Center, Copenhagen Mental Health Services, iPSYCH - The Lundbeck Foundation's Initiative for Integrative Psychiatric Research, Boserupvej, DK-4000, Roskilde, Denmark.
Thomas M WergeInstitute of Biological Psychiatry, Sct. Hans Mental Health Center, Copenhagen Mental Health Services, iPSYCH - The Lundbeck Foundation's Initiative for Integrative Psychiatric Research, Boserupvej, DK-4000, Roskilde, Denmark.
Patricia A BrennanDepartment of Psychology, Emory University, Atlanta, GA, USA.
Joseph F CubellsGenetics and Molecular Biology Program, Emory University, Atlanta, GA, USA.
D Jeffrey NewportDepartments of Psychiatry & Behavioral Sciences and Obstetrics & Gynecology, University of Miami Miller School of Medicine, Miami, FL, USA.
Zachary N StoweDepartments of Psychiatry & Behavioral Sciences, Pediatrics, and Obstetrics & Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Jeanie L Y CheongMurdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia.
Philippa DalachMurdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia.
Lex W DoyleMurdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia.
Yuk J LokeMurdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia.
Andrea A BaccarelliLaboratory of Environmental Precision Biosciences, Columbia University Mailman School of Public Health, New York, NY, USA.
Allan C JustDepartment of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Robert O WrightDepartment of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Mara M Téllez-RojoCenter for Nutrition and Health Research, National Institute of Public Health, Cuernavaca, Morelos, Mexico.
Katherine SvenssonDepartment of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Letizia TrevisiDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Elizabeth M KennedyGenetics and Molecular Biology Program, Emory University, Atlanta, GA, USA.
Elisabeth B BinderDepartment of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Stella IuratoDepartment of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany.
Darina CzamaraDepartment of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany.
Katri RäikkönenInstitute of Behavioral Sciences, University of Helsinki, 00014, Helsinki, Finland.
Jari M T LahtiInstitute of Behavioral Sciences, University of Helsinki, 00014, Helsinki, Finland.
Anu-Katriina PesonenInstitute of Behavioral Sciences, University of Helsinki, 00014, Helsinki, Finland.
Eero KajantieNational Institute for Health and Welfare, Children's Hospital, Helsinki University Hospital, 00271, Helsinki, Finland.
Pia M VillaObstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, 00014, Helsinki, Finland.
Hannele LaivuoriMedical and Clinical Genetics, and Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, 00014, Helsinki, Finland.
Esa HämäläinenHUSLAB and Department of Clinical Chemistry, Helsinki University Central Hospital, 00014, Helsinki, Finland.
Hea Jin ParkDepartment of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, US.
Lynn B BaileyDepartment of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, US.
Sasha E ParetsDepartment of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Varun KilaruDepartment of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, US.
Ramkumar MenonDepartment of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, US.
Steve HorvathDepartment of Human Genetics, David Geffen School of Medicine University of California Los Angeles, Los Angeles, CA, 90095, US.
Nicole R BushDepartment of Psychiatry, University of California, San Francisco, CA, US.
Kaja Z LeWinnDepartment of Psychiatry, University of California, San Francisco, CA, US.
Frances A TylavskyDepartment of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, US.
Karen N ConneelyGenetics and Molecular Biology Program, Emory University, Atlanta, GA, USA.
Alicia K SmithGenetics and Molecular Biology Program, Emory University, Atlanta, GA, USA. alicia.smith@emory.edu.ORCID 0000-0002-8537-5156

Funding

The Mount Sinai Transdisciplinary Center on Early Environmental ExposuresP30ES023515 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Robert O Wright · 2014 to 2026
$21.3M
The Impact of Maternal Depression, Anxiety, and StressP50MH077928 · NIMH · EMORY UNIVERSITY · PI STOWE, ZACHARY N · 2007 to 2011
$9.6M
Graduate and Postdoctoral Training in ToxicologyT32ES012870 · NIEHS · EMORY UNIVERSITY · PI Carmen Joseph Marsit · 2004 to 2026
$9.1M
PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM008490 · NIGMS · EMORY UNIVERSITY · PI BOSS, JEREMY M. · 1993 to 2022
$8.0M
BPA, Phthalates & Stress: Mechanisms and Interactions for Childhood ObesityR01ES021357 · NIEHS · HARVARD SCHOOL OF PUBLIC HEALTH · PI BACCARELLI, ANDREA, WRIGHT, ROBERT O · 2012 to 2016
$3.3M
Environment, Fetal Tissue DNA Methylation & BirthweightR01ES020268 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BACCARELLI, ANDREA, WRIGHT, ROBERT O · 2011 to 2013
$2.5M
Epigenetic and Biobehavioral Determinants of Preterm Birth in Black WomenR01MD009064 · NIMHD · EMORY UNIVERSITY · PI DUNLOP, ANNE LANG, SMITH, ALICIA K · 2014 to 2018
$1.9M
Epigenetic Biomarkers of Early Psychotropic Medication ExposureRC1MH088609 · NIMH · EMORY UNIVERSITY · PI BRENNAN, PATRICIA A, SMITH, ALICIA K · 2009 to 2010
$982k
The epiGenetIcs Leads to aGe-relAted diseases (GILGA-mesh) NetworkU34AG051425 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HORVATH, STEVE · 2015 to 2017
$954k
Prenatal Exposure to Endocrine Disrupters, DNA Methylation, and Childhood ObesityR00ES023450 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JUST, ALLAN C. · 2016 to 2018
$747k
Prenatal Exposure to Endocrine Disrupters, DNA Methylation, and Childhood ObesityK99ES023450 · NIEHS · HARVARD SCHOOL OF PUBLIC HEALTH · PI JUST, ALLAN C. · 2014 to 2015
$163k
NIA NIH HHS U34 AG051425NIEHS NIH HHS K99 ES023450NIEHS NIH HHS P30 ES023515NIEHS NIH HHS R00 ES023450NIEHS NIH HHS R01 ES020268NIEHS NIH HHS R01 ES021357NIEHS NIH HHS T32 ES012870NIGMS NIH HHS T32 GM008490NIMHD NIH HHS R01 MD009064NIMH NIH HHS P50 MH077928NIMH NIH HHS RC1 MH088609
6 · The paper itself

Abstract

backgroundGestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth.

resultsWe find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry.

conclusionsDNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.

Indexed as

Gestational AgeAdultAgingBiomarkersBirth WeightCpG IslandsDNA MethylationEpigenesis, GeneticFemaleFetal DevelopmentHumansInfant, NewbornMalePregnancyBiomarkersAgingBiomarkerBirthweightBlood spotCord bloodDevelopmental ageDNA methylationEpigenetic clockFetusMedicaidPreterm birthSocioeconomic status

Identifiers

PMID27717399
PMCPMC5054584

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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.