Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood

Research output: Contribution to journalJournal articlepeer-review

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Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood. / Almstrup, Kristian; Johansen, Marie Lindhardt; Busch, Alexander S.; Hagen, Casper P; Nielsen, John E; Petersen, Jørgen Holm; Juul, Anders.

In: Scientific Reports, Vol. 6, 28657 , 28.06.2016, p. 1-12.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Almstrup, K, Johansen, ML, Busch, AS, Hagen, CP, Nielsen, JE, Petersen, JH & Juul, A 2016, 'Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood', Scientific Reports, vol. 6, 28657 , pp. 1-12. https://doi.org/10.1038/srep28657, https://doi.org/10.1038/srep30664

APA

Almstrup, K., Johansen, M. L., Busch, A. S., Hagen, C. P., Nielsen, J. E., Petersen, J. H., & Juul, A. (2016). Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood. Scientific Reports, 6, 1-12. [28657 ]. https://doi.org/10.1038/srep28657, https://doi.org/10.1038/srep30664

Vancouver

Almstrup K, Johansen ML, Busch AS, Hagen CP, Nielsen JE, Petersen JH et al. Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood. Scientific Reports. 2016 Jun 28;6:1-12. 28657 . https://doi.org/10.1038/srep28657, https://doi.org/10.1038/srep30664

Author

Almstrup, Kristian ; Johansen, Marie Lindhardt ; Busch, Alexander S. ; Hagen, Casper P ; Nielsen, John E ; Petersen, Jørgen Holm ; Juul, Anders. / Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood. In: Scientific Reports. 2016 ; Vol. 6. pp. 1-12.

Bibtex

@article{20d75031d65c44f6aacf060d393f2020,
title = "Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood",
abstract = "Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic–pituitary–gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphismsonly explains few months in the large inter-individual variation in the timing of puberty. We have analysed longitudinal genome-wide changes in DNA methylation in peripheral blood samples (n = 102) obtained from 51 healthy children before and after pubertal onset. We show that changes in single methylation sites are tightly associated with physiological pubertal transition and altered reproductive hormone levels. These methylation sites cluster in and around genes enriched for biological functions related to pubertal development. Importantly, we identified that methylation of the genomic region containing the promoter of TRIP6 was co-ordinately regulated as a function of pubertal development. In accordance, immunohistochemistry identified TRIP6 in adult, but not pre-pubertal, testicular Leydig cells and circulating TRIP6 levels doubled during puberty. Using elastic net prediction models, methylation patterns predicted pubertal development more accurately than chronological age. We demonstrate for the first time that pubertal attainment of secondary sexual characteristics is mirrored by changes in DNA methylation patterns in peripheral blood. Thus, modulations of the epigenome seem involved in regulation of the individual pubertal timing.",
author = "Kristian Almstrup and Johansen, {Marie Lindhardt} and Busch, {Alexander S.} and Hagen, {Casper P} and Nielsen, {John E} and Petersen, {J{\o}rgen Holm} and Anders Juul",
note = "Erratum: Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood This Article contains typographical errors in Table 1. In the column {\textquoteleft}Pubertal age{\textquoteright} the values for Boys-pre {\textquoteleft}1st–3rd Qu{\textquoteright} and {\textquoteleft}Range{\textquoteright} “−3.07–1.80” and “−5.06–0.42” should read: “of “−3.07– −1.80” and “−5.06– −0.42” respectively. In addition, the Girls-pre values for {\textquoteleft}1st–3rd Qu{\textquoteright} and {\textquoteleft}Range{\textquoteright} “−2.54–0.85” and “−6.01–0.42” should read: “−2.54– −0.85” and “−6.01– −0.42” respectively.",
year = "2016",
month = jun,
day = "28",
doi = "10.1038/srep28657",
language = "English",
volume = "6",
pages = "1--12",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood

AU - Almstrup, Kristian

AU - Johansen, Marie Lindhardt

AU - Busch, Alexander S.

AU - Hagen, Casper P

AU - Nielsen, John E

AU - Petersen, Jørgen Holm

AU - Juul, Anders

N1 - Erratum: Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood This Article contains typographical errors in Table 1. In the column ‘Pubertal age’ the values for Boys-pre ‘1st–3rd Qu’ and ‘Range’ “−3.07–1.80” and “−5.06–0.42” should read: “of “−3.07– −1.80” and “−5.06– −0.42” respectively. In addition, the Girls-pre values for ‘1st–3rd Qu’ and ‘Range’ “−2.54–0.85” and “−6.01–0.42” should read: “−2.54– −0.85” and “−6.01– −0.42” respectively.

PY - 2016/6/28

Y1 - 2016/6/28

N2 - Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic–pituitary–gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphismsonly explains few months in the large inter-individual variation in the timing of puberty. We have analysed longitudinal genome-wide changes in DNA methylation in peripheral blood samples (n = 102) obtained from 51 healthy children before and after pubertal onset. We show that changes in single methylation sites are tightly associated with physiological pubertal transition and altered reproductive hormone levels. These methylation sites cluster in and around genes enriched for biological functions related to pubertal development. Importantly, we identified that methylation of the genomic region containing the promoter of TRIP6 was co-ordinately regulated as a function of pubertal development. In accordance, immunohistochemistry identified TRIP6 in adult, but not pre-pubertal, testicular Leydig cells and circulating TRIP6 levels doubled during puberty. Using elastic net prediction models, methylation patterns predicted pubertal development more accurately than chronological age. We demonstrate for the first time that pubertal attainment of secondary sexual characteristics is mirrored by changes in DNA methylation patterns in peripheral blood. Thus, modulations of the epigenome seem involved in regulation of the individual pubertal timing.

AB - Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic–pituitary–gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphismsonly explains few months in the large inter-individual variation in the timing of puberty. We have analysed longitudinal genome-wide changes in DNA methylation in peripheral blood samples (n = 102) obtained from 51 healthy children before and after pubertal onset. We show that changes in single methylation sites are tightly associated with physiological pubertal transition and altered reproductive hormone levels. These methylation sites cluster in and around genes enriched for biological functions related to pubertal development. Importantly, we identified that methylation of the genomic region containing the promoter of TRIP6 was co-ordinately regulated as a function of pubertal development. In accordance, immunohistochemistry identified TRIP6 in adult, but not pre-pubertal, testicular Leydig cells and circulating TRIP6 levels doubled during puberty. Using elastic net prediction models, methylation patterns predicted pubertal development more accurately than chronological age. We demonstrate for the first time that pubertal attainment of secondary sexual characteristics is mirrored by changes in DNA methylation patterns in peripheral blood. Thus, modulations of the epigenome seem involved in regulation of the individual pubertal timing.

UR - https://www.nature.com/articles/srep30664

U2 - 10.1038/srep28657

DO - 10.1038/srep28657

M3 - Journal article

C2 - 27349168

VL - 6

SP - 1

EP - 12

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 28657

ER -

ID: 164110482