Characteristics of epigenetic aging across gestational and perinatal tissues

Linda Dieckmann; Marius Lahti-Pulkkinen; Tuomas Kvist; Jari Lahti; Peter E. DeWitt; Cristiana Cruceanu; Hannele Laivuori; Sara Sammallahti; Pia M. Villa; Sanna Suomalainen-König; Johan G. Eriksson; Eero Kajantie; Katri Raikkönen; Elisabeth B. Binder; Darina Czamara

doi:10.1186/s13148-021-01080-y

Characteristics of epigenetic aging across gestational and perinatal tissues

Linda Dieckmann, Marius Lahti-Pulkkinen, Tuomas Kvist, Jari Lahti, Peter E. DeWitt, Cristiana Cruceanu, Hannele Laivuori, Sara Sammallahti, Pia M. Villa, Sanna Suomalainen-König, Johan G. Eriksson, Eero Kajantie, Katri Raikkönen, Elisabeth B. Binder, Darina Czamara^*

^*Corresponding author for this work

Child and Adolescent Psychiatry / Psychology

Research output: Contribution to journal › Article › Academic › peer-review

31 Citations (Scopus)

Abstract

Background: Epigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age. However, so far, only few studies have examined epigenetic aging in newborns—especially regarding different gestational or perinatal tissues. In this study, we investigated which birth- and pregnancy-related variables are most important in predicting gestational epigenetic age acceleration or deceleration (i.e., the deviation between gestational epigenetic age estimated from the DNA methylome and chronological gestational age) in chorionic villus, placenta and cord blood tissues from two independent study cohorts (ITU, n = 639 and PREDO, n = 966). We further characterized the correspondence of epigenetic age deviations between these tissues. Results: Among the most predictive factors of epigenetic age deviations in single tissues were child sex, birth length, maternal smoking during pregnancy, maternal mental disorders until childbirth, delivery mode and parity. However, the specific factors related to epigenetic age deviation and the direction of association differed across tissues. In individuals with samples available from more than one tissue, relative epigenetic age deviations were not correlated across tissues. Conclusion: Gestational epigenetic age acceleration or deceleration was not related to more favorable or unfavorable factors in one direction in the investigated tissues, and the relative epigenetic age differed between tissues of the same person. This indicates that epigenetic age deviations associate with distinct, tissue specific, factors during the gestational and perinatal period. Our findings suggest that the epigenetic age of the newborn should be seen as a characteristic of a specific tissue, and less as a general characteristic of the child itself.

Original language	English
Article number	97
Journal	Clinical Epigenetics
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/s13148-021-01080-y
Publication status	Published - 29 Apr 2021

Bibliographical note

Funding Information:
Open Access funding enabled and organized by Projekt DEAL. The ITU and the PREDO studies are funded by Academy of Finland (Award Numbers: 284859, 312670, 1324596). The funder had no role in the design of the ITU study, or conduct of the study, collection, management, analysis and interpretation of the data, preparation, review, or approval of the manuscript, or decision to submit the manuscript for publication. ML-P receives funding from the Academy of Finland, University of Helsinki Funds.

Funding Information:
EB is the coinventor of FKBP5: a novel target for antidepressant therapy, European Patent no. EP 1687443 B1, and receives a research grant from Böhringer Ingelheim for a collaboration on functional investigations of FKBP5. Otherwise, the authors declare that they have no competing interests.

Publisher Copyright:
© 2021, The Author(s).

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10.1186/s13148-021-01080-y

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Dieckmann, L., Lahti-Pulkkinen, M., Kvist, T., Lahti, J., DeWitt, P. E., Cruceanu, C., Laivuori, H., Sammallahti, S., Villa, P. M., Suomalainen-König, S., Eriksson, J. G., Kajantie, E., Raikkönen, K., Binder, E. B., & Czamara, D. (2021). Characteristics of epigenetic aging across gestational and perinatal tissues. Clinical Epigenetics, 13(1), Article 97. https://doi.org/10.1186/s13148-021-01080-y

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title = "Characteristics of epigenetic aging across gestational and perinatal tissues",

abstract = "Background: Epigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age. However, so far, only few studies have examined epigenetic aging in newborns—especially regarding different gestational or perinatal tissues. In this study, we investigated which birth- and pregnancy-related variables are most important in predicting gestational epigenetic age acceleration or deceleration (i.e., the deviation between gestational epigenetic age estimated from the DNA methylome and chronological gestational age) in chorionic villus, placenta and cord blood tissues from two independent study cohorts (ITU, n = 639 and PREDO, n = 966). We further characterized the correspondence of epigenetic age deviations between these tissues. Results: Among the most predictive factors of epigenetic age deviations in single tissues were child sex, birth length, maternal smoking during pregnancy, maternal mental disorders until childbirth, delivery mode and parity. However, the specific factors related to epigenetic age deviation and the direction of association differed across tissues. In individuals with samples available from more than one tissue, relative epigenetic age deviations were not correlated across tissues. Conclusion: Gestational epigenetic age acceleration or deceleration was not related to more favorable or unfavorable factors in one direction in the investigated tissues, and the relative epigenetic age differed between tissues of the same person. This indicates that epigenetic age deviations associate with distinct, tissue specific, factors during the gestational and perinatal period. Our findings suggest that the epigenetic age of the newborn should be seen as a characteristic of a specific tissue, and less as a general characteristic of the child itself.",

author = "Linda Dieckmann and Marius Lahti-Pulkkinen and Tuomas Kvist and Jari Lahti and DeWitt, {Peter E.} and Cristiana Cruceanu and Hannele Laivuori and Sara Sammallahti and Villa, {Pia M.} and Sanna Suomalainen-K{\"o}nig and Eriksson, {Johan G.} and Eero Kajantie and Katri Raikk{\"o}nen and Binder, {Elisabeth B.} and Darina Czamara",

note = "Funding Information: Open Access funding enabled and organized by Projekt DEAL. The ITU and the PREDO studies are funded by Academy of Finland (Award Numbers: 284859, 312670, 1324596). The funder had no role in the design of the ITU study, or conduct of the study, collection, management, analysis and interpretation of the data, preparation, review, or approval of the manuscript, or decision to submit the manuscript for publication. ML-P receives funding from the Academy of Finland, University of Helsinki Funds. Funding Information: EB is the coinventor of FKBP5: a novel target for antidepressant therapy, European Patent no. EP 1687443 B1, and receives a research grant from B{\"o}hringer Ingelheim for a collaboration on functional investigations of FKBP5. Otherwise, the authors declare that they have no competing interests. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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Dieckmann, L, Lahti-Pulkkinen, M, Kvist, T, Lahti, J, DeWitt, PE, Cruceanu, C, Laivuori, H, Sammallahti, S, Villa, PM, Suomalainen-König, S, Eriksson, JG, Kajantie, E, Raikkönen, K, Binder, EB & Czamara, D 2021, 'Characteristics of epigenetic aging across gestational and perinatal tissues', Clinical Epigenetics, vol. 13, no. 1, 97. https://doi.org/10.1186/s13148-021-01080-y

TY - JOUR

T1 - Characteristics of epigenetic aging across gestational and perinatal tissues

AU - Dieckmann, Linda

AU - Lahti-Pulkkinen, Marius

AU - Kvist, Tuomas

AU - Lahti, Jari

AU - DeWitt, Peter E.

AU - Cruceanu, Cristiana

AU - Laivuori, Hannele

AU - Sammallahti, Sara

AU - Villa, Pia M.

AU - Suomalainen-König, Sanna

AU - Eriksson, Johan G.

AU - Kajantie, Eero

AU - Raikkönen, Katri

AU - Binder, Elisabeth B.

AU - Czamara, Darina

N1 - Funding Information: Open Access funding enabled and organized by Projekt DEAL. The ITU and the PREDO studies are funded by Academy of Finland (Award Numbers: 284859, 312670, 1324596). The funder had no role in the design of the ITU study, or conduct of the study, collection, management, analysis and interpretation of the data, preparation, review, or approval of the manuscript, or decision to submit the manuscript for publication. ML-P receives funding from the Academy of Finland, University of Helsinki Funds. Funding Information: EB is the coinventor of FKBP5: a novel target for antidepressant therapy, European Patent no. EP 1687443 B1, and receives a research grant from Böhringer Ingelheim for a collaboration on functional investigations of FKBP5. Otherwise, the authors declare that they have no competing interests. Publisher Copyright: © 2021, The Author(s).

PY - 2021/4/29

Y1 - 2021/4/29

N2 - Background: Epigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age. However, so far, only few studies have examined epigenetic aging in newborns—especially regarding different gestational or perinatal tissues. In this study, we investigated which birth- and pregnancy-related variables are most important in predicting gestational epigenetic age acceleration or deceleration (i.e., the deviation between gestational epigenetic age estimated from the DNA methylome and chronological gestational age) in chorionic villus, placenta and cord blood tissues from two independent study cohorts (ITU, n = 639 and PREDO, n = 966). We further characterized the correspondence of epigenetic age deviations between these tissues. Results: Among the most predictive factors of epigenetic age deviations in single tissues were child sex, birth length, maternal smoking during pregnancy, maternal mental disorders until childbirth, delivery mode and parity. However, the specific factors related to epigenetic age deviation and the direction of association differed across tissues. In individuals with samples available from more than one tissue, relative epigenetic age deviations were not correlated across tissues. Conclusion: Gestational epigenetic age acceleration or deceleration was not related to more favorable or unfavorable factors in one direction in the investigated tissues, and the relative epigenetic age differed between tissues of the same person. This indicates that epigenetic age deviations associate with distinct, tissue specific, factors during the gestational and perinatal period. Our findings suggest that the epigenetic age of the newborn should be seen as a characteristic of a specific tissue, and less as a general characteristic of the child itself.

AB - Background: Epigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age. However, so far, only few studies have examined epigenetic aging in newborns—especially regarding different gestational or perinatal tissues. In this study, we investigated which birth- and pregnancy-related variables are most important in predicting gestational epigenetic age acceleration or deceleration (i.e., the deviation between gestational epigenetic age estimated from the DNA methylome and chronological gestational age) in chorionic villus, placenta and cord blood tissues from two independent study cohorts (ITU, n = 639 and PREDO, n = 966). We further characterized the correspondence of epigenetic age deviations between these tissues. Results: Among the most predictive factors of epigenetic age deviations in single tissues were child sex, birth length, maternal smoking during pregnancy, maternal mental disorders until childbirth, delivery mode and parity. However, the specific factors related to epigenetic age deviation and the direction of association differed across tissues. In individuals with samples available from more than one tissue, relative epigenetic age deviations were not correlated across tissues. Conclusion: Gestational epigenetic age acceleration or deceleration was not related to more favorable or unfavorable factors in one direction in the investigated tissues, and the relative epigenetic age differed between tissues of the same person. This indicates that epigenetic age deviations associate with distinct, tissue specific, factors during the gestational and perinatal period. Our findings suggest that the epigenetic age of the newborn should be seen as a characteristic of a specific tissue, and less as a general characteristic of the child itself.

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Characteristics of epigenetic aging across gestational and perinatal tissues

Abstract

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