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; Thomas M Werge; Patricia A Brennan; Joseph F Cubells; D Jeffrey Newport; Zachary N Stowe; Jeanie L Y Cheong; Philippa Dalach; Lex W Doyle; Yuk J Loke; Andrea A Baccarelli; Allan C Just; Robert O Wright; Mara M Téllez-Rojo; Katherine Svensson; Letizia Trevisi; Elizabeth M Kennedy; Elisabeth B Binder; Stella Iurato; Darina Czamara; Katri Räikkönen; Jari M T Lahti; Anu-Katriina Pesonen; Eero Kajantie; Pia M Villa; Hannele Laivuori; Esa Hämäläinen; Hea Jin Park; Lynn B Bailey; Sasha E Parets; Varun Kilaru; Ramkumar Menon; Steve Horvath; Nicole R Bush; Kaja Z LeWinn; Frances A Tylavsky; Karen N Conneely; Alicia K Smith

doi:10.1186/s13059-016-1068-z

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

Journal article

Open access

Peer reviewed

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, …

Genome biology, Vol.17(1), pp.206-206

2016-10-07

DOI: https://doi.org/10.1186/s13059-016-1068-z

PMID: 27717399

Abstract

Adult

Aging - genetics

Biomarkers - blood

Birth Weight

CpG Islands - genetics

DNA Methylation - genetics

Epigenesis, Genetic

Female

Fetal Development - genetics

Gestational Age

Humans

Infant, Newborn

Male

Pregnancy

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. 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. 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.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.54 Molecular & Cell Biology - Genetics; 1.54.100 DNA Methylation
Web Of Science research areas: Biotechnology & Applied Microbiology; Genetics & Heredity
ESI research areas: Molecular Biology & Genetics

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Title: An epigenetic clock for gestational age at birth based on blood methylation data
Creators: Anna K Knight - Genetics and Molecular Biology Program, Emory University, Atlanta, GA, USA
Jeffrey M Craig - Murdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia
Christiane Theda - The Royal Women's Hospital, Murdoch Childrens Research Institute and University of Melbourne, Parkville, Victoria, 3052, Australia
Marie Bækvad-Hansen - Section of Neonatal Genetics, Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark
Jonas Bybjerg-Grauholm - Section of Neonatal Genetics, Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark
Christine S Hansen - Section of Neonatal Genetics, Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark
Mads V Hollegaard - The Danish Neonatal Screening Biobank, Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark
David M Hougaard - The Danish Neonatal Screening Biobank, Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark
Preben B Mortensen - National Centre for Register-based Research, School of Business and Social Sciences, Aarhus University, Fuglesangs Allé 4, 8210, Aarhus V, Denmark
Shantel M Weinsheimer - 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
Thomas M Werge - 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
Patricia A Brennan - Department of Psychology, Emory University, Atlanta, GA, USA
Joseph F Cubells - Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
D Jeffrey Newport - Departments of Psychiatry & Behavioral Sciences and Obstetrics & Gynecology, University of Miami Miller School of Medicine, Miami, FL, USA
Zachary N Stowe - Departments of Psychiatry & Behavioral Sciences, Pediatrics, and Obstetrics & Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Jeanie L Y Cheong - The Royal Women's Hospital, Murdoch Childrens Research Institute and University of Melbourne, Parkville, Victoria, 3052, Australia
Philippa Dalach - Murdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia
Lex W Doyle - The Royal Women's Hospital, Murdoch Childrens Research Institute and University of Melbourne, Parkville, Victoria, 3052, Australia
Yuk J Loke - Murdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia
Andrea A Baccarelli - Laboratory of Environmental Precision Biosciences, Columbia University Mailman School of Public Health, New York, NY, USA
Allan C Just - Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Robert O Wright - Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Mara M Téllez-Rojo - Center for Nutrition and Health Research, National Institute of Public Health, Cuernavaca, Morelos, Mexico
Katherine Svensson - Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Letizia Trevisi - Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Elizabeth M Kennedy - Genetics and Molecular Biology Program, Emory University, Atlanta, GA, USA
Elisabeth B Binder - Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany
Stella Iurato - Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany
Darina Czamara - Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany
Katri Räikkönen - Institute of Behavioral Sciences, University of Helsinki, 00014, Helsinki, Finland
Jari M T Lahti - Folkhälsan Research Centre, Helsinki, Finland
Anu-Katriina Pesonen - Institute of Behavioral Sciences, University of Helsinki, 00014, Helsinki, Finland
Eero Kajantie - Department of Obstetrics and Gynecology, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
Pia M Villa - Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, 00014, Helsinki, Finland
Hannele Laivuori - Institute for Molecular Medicine Finland, University of Helsinki, 00014, Helsinki, Finland
Esa Hämäläinen - HUSLAB and Department of Clinical Chemistry, Helsinki University Central Hospital, 00014, Helsinki, Finland
Hea Jin Park - Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, US
Lynn B Bailey - Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, US
Sasha E Parets - Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
Varun Kilaru - Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, US
Ramkumar Menon - Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, US
Steve Horvath - Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, 90095, US
Nicole R Bush - Department of Pediatrics, University of California, San Francisco, CA, US
Kaja Z LeWinn - Department of Psychiatry, University of California, San Francisco, CA, US
Frances A Tylavsky - Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, US
Karen N Conneely - Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA
Alicia K Smith - Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, US. alicia.smith@emory.edu
Publication Details: Genome biology, Vol.17(1), pp.206-206
Grant note: R00 ES023450 / NIEHS NIH HHS R01 MD009064 / NIMHD NIH HHS K99 ES023450 / NIEHS NIH HHS P50 MH077928 / NIMH NIH HHS T32 GM008490 / NIGMS NIH HHS P30 ES023515 / NIEHS NIH HHS RC1 MH088609 / NIMH NIH HHS T32 ES012870 / NIEHS NIH HHS R01 ES021357 / NIEHS NIH HHS R01 ES020268 / NIEHS NIH HHS U34 AG051425 / NIA NIH HHS
Language: English
Resource Type: Journal article
PMID: 27717399
Record Identifier: 991031615286902976