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

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 BaccarelliAllan 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

Department of Clinical Medicine

80 Citations (Scopus)

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.

Original language	English
Article number	206
Journal	Genome Biology (Online Edition)
Volume	17
Number of pages	11
ISSN	1474-7596
DOIs	https://doi.org/10.1186/s13059-016-1068-z
Publication status	Published - 7 Oct 2016

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Knight, A. K., Craig, J. M., Theda, C., Bækvad-Hansen, M., Bybjerg-Grauholm, J., Hansen, C. S., Hollegaard, M. V., Hougaard, D. M., Mortensen, P. B., Weinsheimer, S. M., Werge, T. M., Brennan, P. A., Cubells, J. F., Newport, D. J., Stowe, Z. N., Cheong, J. L. Y., Dalach, P., Doyle, L. W., Loke, Y. J., ... Smith, A. K. (2016). An epigenetic clock for gestational age at birth based on blood methylation data. Genome Biology (Online Edition), 17, [206]. https://doi.org/10.1186/s13059-016-1068-z

Knight, AK, Craig, JM, Theda, C, Bækvad-Hansen, M, Bybjerg-Grauholm, J, Hansen, CS, Hollegaard, MV, Hougaard, DM, Mortensen, PB, Weinsheimer, SM, Werge, TM, Brennan, PA, Cubells, JF, Newport, DJ, Stowe, ZN, Cheong, JLY, Dalach, P, Doyle, LW, Loke, YJ, Baccarelli, AA, Just, AC, Wright, RO, Téllez-rojo, MM, Svensson, K, Trevisi, L, Kennedy, EM, Binder, EB, Iurato, S, Czamara, D, Räikkönen, K, Lahti, JMT, Pesonen, A, Kajantie, E, Villa, PM, Laivuori, H, Hämäläinen, E, Park, HJ, Bailey, LB, Parets, SE, Kilaru, V, Menon, R, Horvath, S, Bush, NR, Lewinn, KZ, Tylavsky, FA, Conneely, KN & Smith, AK 2016, 'An epigenetic clock for gestational age at birth based on blood methylation data', Genome Biology (Online Edition), vol. 17, 206. https://doi.org/10.1186/s13059-016-1068-z

@article{921d96430a7a4bb396c9b06b610a787c,

title = "An epigenetic clock for gestational age at birth based on blood methylation data",

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.",

author = "Knight, {Anna K.} and Craig, {Jeffrey M} and Christiane Theda and Marie B{\ae}kvad-Hansen and Jonas Bybjerg-Grauholm and Hansen, {Christine S} and Hollegaard, {Mads V} and Hougaard, {David M.} and Mortensen, {Preben B} and Weinsheimer, {Shantel M.} and Werge, {Thomas M.} and Brennan, {Patricia A.} and Cubells, {Joseph F.} and Newport, {D. Jeffrey} and Stowe, {Zachary N.} and Cheong, {Jeanie L. Y.} and Philippa Dalach and Doyle, {Lex W.} and Loke, {Yuk J.} and Baccarelli, {Andrea A} and Just, {Allan C.} and Wright, {Robert O.} and T{\'e}llez-rojo, {Mara M.} and Katherine Svensson and Letizia Trevisi and Kennedy, {Elizabeth M.} and Binder, {Elisabeth B.} and Stella Iurato and Darina Czamara and Katri R{\"a}ikk{\"o}nen and Lahti, {Jari M. T.} and Anu-katriina Pesonen and Eero Kajantie and Villa, {Pia M.} and Hannele Laivuori and Esa H{\"a}m{\"a}l{\"a}inen and Park, {Hea Jin} and Bailey, {Lynn B.} and Parets, {Sasha E.} and Varun Kilaru and Ramkumar Menon and Steve Horvath and Bush, {Nicole R.} and Lewinn, {Kaja Z.} and Tylavsky, {Frances A.} and Conneely, {Karen N.} and Smith, {Alicia K.}",

year = "2016",

month = oct,

day = "7",

doi = "10.1186/s13059-016-1068-z",

language = "English",

volume = "17",

journal = "Genome Biology (Online Edition)",

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TY - JOUR

T1 - An epigenetic clock for gestational age at birth based on blood methylation data

AU - Knight, Anna K.

AU - Craig, Jeffrey M

AU - Theda, Christiane

AU - Bækvad-Hansen, Marie

AU - Bybjerg-Grauholm, Jonas

AU - Hansen, Christine S

AU - Hollegaard, Mads V

AU - Hougaard, David M.

AU - Mortensen, Preben B

AU - Weinsheimer, Shantel M.

AU - Werge, Thomas M.

AU - Brennan, Patricia A.

AU - Cubells, Joseph F.

AU - Newport, D. Jeffrey

AU - Stowe, Zachary N.

AU - Cheong, Jeanie L. Y.

AU - Dalach, Philippa

AU - Doyle, Lex W.

AU - Loke, Yuk J.

AU - Baccarelli, Andrea A

AU - Just, Allan C.

AU - Wright, Robert O.

AU - Téllez-rojo, Mara M.

AU - Svensson, Katherine

AU - Trevisi, Letizia

AU - Kennedy, Elizabeth M.

AU - Binder, Elisabeth B.

AU - Iurato, Stella

AU - Czamara, Darina

AU - Räikkönen, Katri

AU - Lahti, Jari M. T.

AU - Pesonen, Anu-katriina

AU - Kajantie, Eero

AU - Villa, Pia M.

AU - Laivuori, Hannele

AU - Hämäläinen, Esa

AU - Park, Hea Jin

AU - Bailey, Lynn B.

AU - Parets, Sasha E.

AU - Kilaru, Varun

AU - Menon, Ramkumar

AU - Horvath, Steve

AU - Bush, Nicole R.

AU - Lewinn, Kaja Z.

AU - Tylavsky, Frances A.

AU - Conneely, Karen N.

AU - Smith, Alicia K.

PY - 2016/10/7

Y1 - 2016/10/7

N2 - 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.

AB - 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.

U2 - 10.1186/s13059-016-1068-z

DO - 10.1186/s13059-016-1068-z

M3 - Journal article

C2 - 27717399

SN - 1474-7596

VL - 17

JO - Genome Biology (Online Edition)

JF - Genome Biology (Online Edition)

M1 - 206

ER -

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

Abstract

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