Choice of surrogate tissue influences neonatal EWAS findings

Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 . Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Xinyi Lin [verfasserIn] Ai Ling Teh [verfasserIn] Li Chen [verfasserIn] Ives Yubin Lim [verfasserIn] Pei Fang Tan [verfasserIn] Julia L. MacIsaac [verfasserIn] Alexander M. Morin [verfasserIn] Fabian Yap [verfasserIn] Kok Hian Tan [verfasserIn] Seang Mei Saw [verfasserIn] Yung Seng Lee [verfasserIn] Joanna D. Holbrook [verfasserIn] Keith M. Godfrey [verfasserIn] Michael J. Meaney [verfasserIn] Michael S. Kobor [verfasserIn] Yap Seng Chong [verfasserIn] Peter D. Gluckman [verfasserIn] Neerja Karnani [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	Epigenome-wide association study Tissue-specificity DNA methylation Prenatal factors Genotype Neonate

Übergeordnetes Werk:	In: BMC Medicine - BMC, 2003, 15(2017), 1, Seite 13
Übergeordnetes Werk:	volume:15 ; year:2017 ; number:1 ; pages:13

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12916-017-0970-x

Katalog-ID:	DOAJ071311394

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245	1	0	\|a Choice of surrogate tissue influences neonatal EWAS findings
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520			\|a Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .
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700	0		\|a Ives Yubin Lim \|e verfasserin \|4 aut
700	0		\|a Pei Fang Tan \|e verfasserin \|4 aut
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700	0		\|a Neerja Karnani \|e verfasserin \|4 aut
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allfields	10.1186/s12916-017-0970-x doi (DE-627)DOAJ071311394 (DE-599)DOAJ37cb220187a940d19132b0a92f42c521 DE-627 ger DE-627 rakwb eng Xinyi Lin verfasserin aut Choice of surrogate tissue influences neonatal EWAS findings 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 . Epigenome-wide association study Tissue-specificity DNA methylation Prenatal factors Genotype Neonate Medicine R Ai Ling Teh verfasserin aut Li Chen verfasserin aut Ives Yubin Lim verfasserin aut Pei Fang Tan verfasserin aut Julia L. MacIsaac verfasserin aut Alexander M. Morin verfasserin aut Fabian Yap verfasserin aut Kok Hian Tan verfasserin aut Seang Mei Saw verfasserin aut Yung Seng Lee verfasserin aut Joanna D. Holbrook verfasserin aut Keith M. Godfrey verfasserin aut Michael J. Meaney verfasserin aut Michael S. Kobor verfasserin aut Yap Seng Chong verfasserin aut Peter D. Gluckman verfasserin aut Neerja Karnani verfasserin aut In BMC Medicine BMC, 2003 15(2017), 1, Seite 13 (DE-627)377271225 (DE-600)2131669-7 17417015 nnns volume:15 year:2017 number:1 pages:13 https://doi.org/10.1186/s12916-017-0970-x kostenfrei https://doaj.org/article/37cb220187a940d19132b0a92f42c521 kostenfrei http://link.springer.com/article/10.1186/s12916-017-0970-x kostenfrei https://doaj.org/toc/1741-7015 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2017 1 13
spelling	10.1186/s12916-017-0970-x doi (DE-627)DOAJ071311394 (DE-599)DOAJ37cb220187a940d19132b0a92f42c521 DE-627 ger DE-627 rakwb eng Xinyi Lin verfasserin aut Choice of surrogate tissue influences neonatal EWAS findings 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 . Epigenome-wide association study Tissue-specificity DNA methylation Prenatal factors Genotype Neonate Medicine R Ai Ling Teh verfasserin aut Li Chen verfasserin aut Ives Yubin Lim verfasserin aut Pei Fang Tan verfasserin aut Julia L. MacIsaac verfasserin aut Alexander M. Morin verfasserin aut Fabian Yap verfasserin aut Kok Hian Tan verfasserin aut Seang Mei Saw verfasserin aut Yung Seng Lee verfasserin aut Joanna D. Holbrook verfasserin aut Keith M. Godfrey verfasserin aut Michael J. Meaney verfasserin aut Michael S. Kobor verfasserin aut Yap Seng Chong verfasserin aut Peter D. Gluckman verfasserin aut Neerja Karnani verfasserin aut In BMC Medicine BMC, 2003 15(2017), 1, Seite 13 (DE-627)377271225 (DE-600)2131669-7 17417015 nnns volume:15 year:2017 number:1 pages:13 https://doi.org/10.1186/s12916-017-0970-x kostenfrei https://doaj.org/article/37cb220187a940d19132b0a92f42c521 kostenfrei http://link.springer.com/article/10.1186/s12916-017-0970-x kostenfrei https://doaj.org/toc/1741-7015 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2017 1 13
allfields_unstemmed	10.1186/s12916-017-0970-x doi (DE-627)DOAJ071311394 (DE-599)DOAJ37cb220187a940d19132b0a92f42c521 DE-627 ger DE-627 rakwb eng Xinyi Lin verfasserin aut Choice of surrogate tissue influences neonatal EWAS findings 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 . Epigenome-wide association study Tissue-specificity DNA methylation Prenatal factors Genotype Neonate Medicine R Ai Ling Teh verfasserin aut Li Chen verfasserin aut Ives Yubin Lim verfasserin aut Pei Fang Tan verfasserin aut Julia L. MacIsaac verfasserin aut Alexander M. Morin verfasserin aut Fabian Yap verfasserin aut Kok Hian Tan verfasserin aut Seang Mei Saw verfasserin aut Yung Seng Lee verfasserin aut Joanna D. Holbrook verfasserin aut Keith M. Godfrey verfasserin aut Michael J. Meaney verfasserin aut Michael S. Kobor verfasserin aut Yap Seng Chong verfasserin aut Peter D. Gluckman verfasserin aut Neerja Karnani verfasserin aut In BMC Medicine BMC, 2003 15(2017), 1, Seite 13 (DE-627)377271225 (DE-600)2131669-7 17417015 nnns volume:15 year:2017 number:1 pages:13 https://doi.org/10.1186/s12916-017-0970-x kostenfrei https://doaj.org/article/37cb220187a940d19132b0a92f42c521 kostenfrei http://link.springer.com/article/10.1186/s12916-017-0970-x kostenfrei https://doaj.org/toc/1741-7015 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2017 1 13
allfieldsGer	10.1186/s12916-017-0970-x doi (DE-627)DOAJ071311394 (DE-599)DOAJ37cb220187a940d19132b0a92f42c521 DE-627 ger DE-627 rakwb eng Xinyi Lin verfasserin aut Choice of surrogate tissue influences neonatal EWAS findings 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 . Epigenome-wide association study Tissue-specificity DNA methylation Prenatal factors Genotype Neonate Medicine R Ai Ling Teh verfasserin aut Li Chen verfasserin aut Ives Yubin Lim verfasserin aut Pei Fang Tan verfasserin aut Julia L. MacIsaac verfasserin aut Alexander M. Morin verfasserin aut Fabian Yap verfasserin aut Kok Hian Tan verfasserin aut Seang Mei Saw verfasserin aut Yung Seng Lee verfasserin aut Joanna D. Holbrook verfasserin aut Keith M. Godfrey verfasserin aut Michael J. Meaney verfasserin aut Michael S. Kobor verfasserin aut Yap Seng Chong verfasserin aut Peter D. Gluckman verfasserin aut Neerja Karnani verfasserin aut In BMC Medicine BMC, 2003 15(2017), 1, Seite 13 (DE-627)377271225 (DE-600)2131669-7 17417015 nnns volume:15 year:2017 number:1 pages:13 https://doi.org/10.1186/s12916-017-0970-x kostenfrei https://doaj.org/article/37cb220187a940d19132b0a92f42c521 kostenfrei http://link.springer.com/article/10.1186/s12916-017-0970-x kostenfrei https://doaj.org/toc/1741-7015 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2017 1 13
allfieldsSound	10.1186/s12916-017-0970-x doi (DE-627)DOAJ071311394 (DE-599)DOAJ37cb220187a940d19132b0a92f42c521 DE-627 ger DE-627 rakwb eng Xinyi Lin verfasserin aut Choice of surrogate tissue influences neonatal EWAS findings 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 . Epigenome-wide association study Tissue-specificity DNA methylation Prenatal factors Genotype Neonate Medicine R Ai Ling Teh verfasserin aut Li Chen verfasserin aut Ives Yubin Lim verfasserin aut Pei Fang Tan verfasserin aut Julia L. MacIsaac verfasserin aut Alexander M. Morin verfasserin aut Fabian Yap verfasserin aut Kok Hian Tan verfasserin aut Seang Mei Saw verfasserin aut Yung Seng Lee verfasserin aut Joanna D. Holbrook verfasserin aut Keith M. Godfrey verfasserin aut Michael J. Meaney verfasserin aut Michael S. Kobor verfasserin aut Yap Seng Chong verfasserin aut Peter D. Gluckman verfasserin aut Neerja Karnani verfasserin aut In BMC Medicine BMC, 2003 15(2017), 1, Seite 13 (DE-627)377271225 (DE-600)2131669-7 17417015 nnns volume:15 year:2017 number:1 pages:13 https://doi.org/10.1186/s12916-017-0970-x kostenfrei https://doaj.org/article/37cb220187a940d19132b0a92f42c521 kostenfrei http://link.springer.com/article/10.1186/s12916-017-0970-x kostenfrei https://doaj.org/toc/1741-7015 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2017 1 13
language	English
source	In BMC Medicine 15(2017), 1, Seite 13 volume:15 year:2017 number:1 pages:13
sourceStr	In BMC Medicine 15(2017), 1, Seite 13 volume:15 year:2017 number:1 pages:13
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Epigenome-wide association study Tissue-specificity DNA methylation Prenatal factors Genotype Neonate Medicine R
isfreeaccess_bool	true
container_title	BMC Medicine
authorswithroles_txt_mv	Xinyi Lin @@aut@@ Ai Ling Teh @@aut@@ Li Chen @@aut@@ Ives Yubin Lim @@aut@@ Pei Fang Tan @@aut@@ Julia L. MacIsaac @@aut@@ Alexander M. Morin @@aut@@ Fabian Yap @@aut@@ Kok Hian Tan @@aut@@ Seang Mei Saw @@aut@@ Yung Seng Lee @@aut@@ Joanna D. Holbrook @@aut@@ Keith M. Godfrey @@aut@@ Michael J. Meaney @@aut@@ Michael S. Kobor @@aut@@ Yap Seng Chong @@aut@@ Peter D. Gluckman @@aut@@ Neerja Karnani @@aut@@
publishDateDaySort_date	2017-01-01T00:00:00Z
hierarchy_top_id	377271225
id	DOAJ071311394
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ071311394</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230309101115.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2017 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s12916-017-0970-x</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ071311394</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ37cb220187a940d19132b0a92f42c521</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Xinyi Lin</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Choice of surrogate tissue influences neonatal EWAS findings</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Epigenome-wide association study</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tissue-specificity</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA methylation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Prenatal factors</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genotype</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Neonate</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ai Ling Teh</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Li Chen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ives Yubin Lim</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pei Fang Tan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Julia L. MacIsaac</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alexander M. 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author	Xinyi Lin
spellingShingle	Xinyi Lin misc Epigenome-wide association study misc Tissue-specificity misc DNA methylation misc Prenatal factors misc Genotype misc Neonate misc Medicine misc R Choice of surrogate tissue influences neonatal EWAS findings
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topic_title	Choice of surrogate tissue influences neonatal EWAS findings Epigenome-wide association study Tissue-specificity DNA methylation Prenatal factors Genotype Neonate
topic	misc Epigenome-wide association study misc Tissue-specificity misc DNA methylation misc Prenatal factors misc Genotype misc Neonate misc Medicine misc R
topic_unstemmed	misc Epigenome-wide association study misc Tissue-specificity misc DNA methylation misc Prenatal factors misc Genotype misc Neonate misc Medicine misc R
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title	Choice of surrogate tissue influences neonatal EWAS findings
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title_full	Choice of surrogate tissue influences neonatal EWAS findings
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author_browse	Xinyi Lin Ai Ling Teh Li Chen Ives Yubin Lim Pei Fang Tan Julia L. MacIsaac Alexander M. Morin Fabian Yap Kok Hian Tan Seang Mei Saw Yung Seng Lee Joanna D. Holbrook Keith M. Godfrey Michael J. Meaney Michael S. Kobor Yap Seng Chong Peter D. Gluckman Neerja Karnani
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title_sort	choice of surrogate tissue influences neonatal ewas findings
title_auth	Choice of surrogate tissue influences neonatal EWAS findings
abstract	Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .
abstractGer	Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .
abstract_unstemmed	Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .
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title_short	Choice of surrogate tissue influences neonatal EWAS findings
url	https://doi.org/10.1186/s12916-017-0970-x https://doaj.org/article/37cb220187a940d19132b0a92f42c521 http://link.springer.com/article/10.1186/s12916-017-0970-x https://doaj.org/toc/1741-7015
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author2	Ai Ling Teh Li Chen Ives Yubin Lim Pei Fang Tan Julia L. MacIsaac Alexander M. Morin Fabian Yap Kok Hian Tan Seang Mei Saw Yung Seng Lee Joanna D. Holbrook Keith M. Godfrey Michael J. Meaney Michael S. Kobor Yap Seng Chong Peter D. Gluckman Neerja Karnani
author2Str	Ai Ling Teh Li Chen Ives Yubin Lim Pei Fang Tan Julia L. MacIsaac Alexander M. Morin Fabian Yap Kok Hian Tan Seang Mei Saw Yung Seng Lee Joanna D. Holbrook Keith M. Godfrey Michael J. Meaney Michael S. Kobor Yap Seng Chong Peter D. Gluckman Neerja Karnani
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up_date	2024-07-03T19:34:54.614Z
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To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. 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Choice of surrogate tissue influences neonatal EWAS findings

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