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Genome Biol. 2016 Oct 7;17(1):206.

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

Author information

1
Genetics and Molecular Biology Program, Emory University, Atlanta, GA, USA.
2
Murdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia.
3
The Royal Women's Hospital, Murdoch Childrens Research Institute and University of Melbourne, Parkville, Victoria, 3052, Australia.
4
Section of Neonatal Genetics, Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark.
5
The Danish Neonatal Screening Biobank, Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark.
6
National Centre for Register-based Research, School of Business and Social Sciences, Aarhus University, Fuglesangs Allé 4, 8210, Aarhus V, Denmark.
7
Institute 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.
8
Department of Psychology, Emory University, Atlanta, GA, USA.
9
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
10
Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
11
Departments of Psychiatry & Behavioral Sciences and Obstetrics & Gynecology, University of Miami Miller School of Medicine, Miami, FL, USA.
12
Departments of Psychiatry & Behavioral Sciences, Pediatrics, and Obstetrics & Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
13
Laboratory of Environmental Precision Biosciences, Columbia University Mailman School of Public Health, New York, NY, USA.
14
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
15
Center for Nutrition and Health Research, National Institute of Public Health, Cuernavaca, Morelos, Mexico.
16
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
17
Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany.
18
Institute of Behavioral Sciences, University of Helsinki, 00014, Helsinki, Finland.
19
Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.
20
Folkhälsan Research Centre, Helsinki, Finland.
21
National Institute for Health and Welfare, Children's Hospital, Helsinki University Hospital, 00271, Helsinki, Finland.
22
University of Helsinki, 00029, Helsinki, Finland.
23
Department of Obstetrics and Gynecology, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
24
Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, 00014, Helsinki, Finland.
25
Medical and Clinical Genetics, and Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, 00014, Helsinki, Finland.
26
Institute for Molecular Medicine Finland, University of Helsinki, 00014, Helsinki, Finland.
27
HUSLAB and Department of Clinical Chemistry, Helsinki University Central Hospital, 00014, Helsinki, Finland.
28
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, US.
29
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, US.
30
Department of Human Genetics, David Geffen School of Medicine University of California Los Angeles, Los Angeles, CA, 90095, US.
31
Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, 90095, US.
32
Department of Psychiatry, University of California, San Francisco, CA, US.
33
Department of Pediatrics, University of California, San Francisco, CA, US.
34
Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, US.
35
Genetics and Molecular Biology Program, Emory University, Atlanta, GA, USA. alicia.smith@emory.edu.
36
Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. alicia.smith@emory.edu.
37
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, US. alicia.smith@emory.edu.

Abstract

BACKGROUND:

Gestational 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.

RESULTS:

We 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.

CONCLUSIONS:

DNA 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.

KEYWORDS:

Aging; Biomarker; Birthweight; Blood spot; Cord blood; DNA methylation; Developmental age; Epigenetic clock; Fetus; Medicaid; Preterm birth; Socioeconomic status

PMID:
27717399
PMCID:
PMC5054584
DOI:
10.1186/s13059-016-1068-z
[Indexed for MEDLINE]
Free PMC Article

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