Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course

Herman T den Dekker; Kimberley Burrows; Janine F Felix; Lucas A Salas; Ivana Nedeljkovic; Jin Yao; Sheryl L Rifas-Shiman; Carlos Ruiz-Arenas; N Amin; Mariona Bustamante; Dawn L DeMeo; A John Henderson; Caitlin G Howe; Marie-France Hivert; M Arfan Ikram; Johan C de Jongste; Lies Lahousse; Pooja R Mandaviya; Joyce B van Meurs; Mariona Pinart; Gemma C Sharp; Lisette Stolk; André G Uitterlinden; Josep M Anto; Augusto A Litonjua; Carrie V Breton; Guy G Brusselle; Jordi Sunyer; George Davey Smith; Caroline L Relton; Vincent W V Jaddoe; Liesbeth Duijts

doi:10.1183/13993003.01795-2018

Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course

Herman T den Dekker, Kimberley Burrows, Janine F Felix, Lucas A Salas, Ivana Nedeljkovic, Jin Yao, Sheryl L Rifas-Shiman, Carlos Ruiz-Arenas, N Amin, Mariona Bustamante, Dawn L DeMeo, A John Henderson, Caitlin G Howe, Marie-France Hivert, M Arfan Ikram, Johan C de Jongste, Lies Lahousse, Pooja R Mandaviya, Joyce B van Meurs, Mariona PinartGemma C Sharp, Lisette Stolk, André G Uitterlinden, Josep M Anto, Augusto A Litonjua, Carrie V Breton, Guy G Brusselle, Jordi Sunyer, George Davey Smith, Caroline L Relton, Vincent W V Jaddoe, Liesbeth Duijts

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

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Abstract

RATIONALE: We aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course.

METHODS: We meta-analyzed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to Forced Expiratory Volume in 1 s (FEV1), FEV1/Forced Vital Capacity (FVC), and Forced Expiratory Flow at 75% of FVC (FEF75) at ages 7-13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes.

RESULTS: We identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and 9 with COPD in adulthood. Genes annotated to the top ten identified DMRs were HOXA5, PAOX, LINC00602, ABCA7, PER3, CLCA1, VENTX, NUDT12, PTPRN2 and TCL1A. Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways.

INTERPRETATION: Our findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course.

Original language	English
Article number	1801795
Journal	European Respiratory Journal
Volume	53
Issue number	4
Early online date	4 Apr 2019
DOIs	https://doi.org/10.1183/13993003.01795-2018
Publication status	Published - Apr 2019

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den Dekker, H. T., Burrows, K., Felix, J. F., Salas, L. A., Nedeljkovic, I., Yao, J., Rifas-Shiman, S. L., Ruiz-Arenas, C., Amin, N., Bustamante, M., DeMeo, D. L., John Henderson, A., Howe, C. G., Hivert, M-F., Arfan Ikram, M., de Jongste, J. C., Lahousse, L., Mandaviya, P. R., van Meurs, J. B., ... Duijts, L. (2019). Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course. European Respiratory Journal, 53(4), [1801795]. https://doi.org/10.1183/13993003.01795-2018

den Dekker, Herman T ; Burrows, Kimberley ; Felix, Janine F ; Salas, Lucas A ; Nedeljkovic, Ivana ; Yao, Jin ; Rifas-Shiman, Sheryl L ; Ruiz-Arenas, Carlos ; Amin, N ; Bustamante, Mariona ; DeMeo, Dawn L ; John Henderson, A ; Howe, Caitlin G ; Hivert, Marie-France ; Arfan Ikram, M ; de Jongste, Johan C ; Lahousse, Lies ; Mandaviya, Pooja R ; van Meurs, Joyce B ; Pinart, Mariona ; Sharp, Gemma C ; Stolk, Lisette ; Uitterlinden, André G ; Anto, Josep M ; Litonjua, Augusto A ; Breton, Carrie V ; Brusselle, Guy G ; Sunyer, Jordi ; Smith, George Davey ; Relton, Caroline L ; Jaddoe, Vincent W V ; Duijts, Liesbeth. / Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course. In: European Respiratory Journal. 2019 ; Vol. 53, No. 4.

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title = "Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course",

abstract = "RATIONALE: We aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course.METHODS: We meta-analyzed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to Forced Expiratory Volume in 1 s (FEV1), FEV1/Forced Vital Capacity (FVC), and Forced Expiratory Flow at 75% of FVC (FEF75) at ages 7-13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes.RESULTS: We identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and 9 with COPD in adulthood. Genes annotated to the top ten identified DMRs were HOXA5, PAOX, LINC00602, ABCA7, PER3, CLCA1, VENTX, NUDT12, PTPRN2 and TCL1A. Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways.INTERPRETATION: Our findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course.",

author = "{den Dekker}, {Herman T} and Kimberley Burrows and Felix, {Janine F} and Salas, {Lucas A} and Ivana Nedeljkovic and Jin Yao and Rifas-Shiman, {Sheryl L} and Carlos Ruiz-Arenas and N Amin and Mariona Bustamante and DeMeo, {Dawn L} and {John Henderson}, A and Howe, {Caitlin G} and Marie-France Hivert and {Arfan Ikram}, M and {de Jongste}, {Johan C} and Lies Lahousse and Mandaviya, {Pooja R} and {van Meurs}, {Joyce B} and Mariona Pinart and Sharp, {Gemma C} and Lisette Stolk and Uitterlinden, {Andr{\'e} G} and Anto, {Josep M} and Litonjua, {Augusto A} and Breton, {Carrie V} and Brusselle, {Guy G} and Jordi Sunyer and Smith, {George Davey} and Relton, {Caroline L} and Jaddoe, {Vincent W V} and Liesbeth Duijts",

note = "Copyright {\textcopyright}ERS 2019.",

year = "2019",

month = apr,

doi = "10.1183/13993003.01795-2018",

language = "English",

volume = "53",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "4",

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den Dekker, HT, Burrows, K, Felix, JF, Salas, LA, Nedeljkovic, I, Yao, J, Rifas-Shiman, SL, Ruiz-Arenas, C, Amin, N, Bustamante, M, DeMeo, DL, John Henderson, A, Howe, CG, Hivert, M-F, Arfan Ikram, M, de Jongste, JC, Lahousse, L, Mandaviya, PR, van Meurs, JB, Pinart, M, Sharp, GC, Stolk, L, Uitterlinden, AG, Anto, JM, Litonjua, AA, Breton, CV, Brusselle, GG, Sunyer, J, Smith, GD , Relton, CL, Jaddoe, VWV & Duijts, L 2019, 'Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course', European Respiratory Journal, vol. 53, no. 4, 1801795. https://doi.org/10.1183/13993003.01795-2018

Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course. / den Dekker, Herman T; Burrows, Kimberley; Felix, Janine F; Salas, Lucas A; Nedeljkovic, Ivana; Yao, Jin; Rifas-Shiman, Sheryl L; Ruiz-Arenas, Carlos; Amin, N; Bustamante, Mariona; DeMeo, Dawn L; John Henderson, A; Howe, Caitlin G; Hivert, Marie-France; Arfan Ikram, M; de Jongste, Johan C; Lahousse, Lies; Mandaviya, Pooja R; van Meurs, Joyce B; Pinart, Mariona; Sharp, Gemma C; Stolk, Lisette; Uitterlinden, André G; Anto, Josep M; Litonjua, Augusto A; Breton, Carrie V; Brusselle, Guy G; Sunyer, Jordi; Smith, George Davey ; Relton, Caroline L; Jaddoe, Vincent W V; Duijts, Liesbeth.

In: European Respiratory Journal, Vol. 53, No. 4, 1801795, 04.2019.

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

TY - JOUR

T1 - Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course

AU - den Dekker, Herman T

AU - Burrows, Kimberley

AU - Felix, Janine F

AU - Salas, Lucas A

AU - Nedeljkovic, Ivana

AU - Yao, Jin

AU - Rifas-Shiman, Sheryl L

AU - Ruiz-Arenas, Carlos

AU - Amin, N

AU - Bustamante, Mariona

AU - DeMeo, Dawn L

AU - John Henderson, A

AU - Howe, Caitlin G

AU - Hivert, Marie-France

AU - Arfan Ikram, M

AU - de Jongste, Johan C

AU - Lahousse, Lies

AU - Mandaviya, Pooja R

AU - van Meurs, Joyce B

AU - Pinart, Mariona

AU - Sharp, Gemma C

AU - Stolk, Lisette

AU - Uitterlinden, André G

AU - Anto, Josep M

AU - Litonjua, Augusto A

AU - Breton, Carrie V

AU - Brusselle, Guy G

AU - Sunyer, Jordi

AU - Smith, George Davey

AU - Relton, Caroline L

AU - Jaddoe, Vincent W V

AU - Duijts, Liesbeth

PY - 2019/4

Y1 - 2019/4

N2 - RATIONALE: We aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course.METHODS: We meta-analyzed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to Forced Expiratory Volume in 1 s (FEV1), FEV1/Forced Vital Capacity (FVC), and Forced Expiratory Flow at 75% of FVC (FEF75) at ages 7-13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes.RESULTS: We identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and 9 with COPD in adulthood. Genes annotated to the top ten identified DMRs were HOXA5, PAOX, LINC00602, ABCA7, PER3, CLCA1, VENTX, NUDT12, PTPRN2 and TCL1A. Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways.INTERPRETATION: Our findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course.

AB - RATIONALE: We aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course.METHODS: We meta-analyzed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to Forced Expiratory Volume in 1 s (FEV1), FEV1/Forced Vital Capacity (FVC), and Forced Expiratory Flow at 75% of FVC (FEF75) at ages 7-13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes.RESULTS: We identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and 9 with COPD in adulthood. Genes annotated to the top ten identified DMRs were HOXA5, PAOX, LINC00602, ABCA7, PER3, CLCA1, VENTX, NUDT12, PTPRN2 and TCL1A. Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways.INTERPRETATION: Our findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course.

UR - http://www.scopus.com/inward/record.url?scp=85061964595&partnerID=8YFLogxK

U2 - 10.1183/13993003.01795-2018

DO - 10.1183/13993003.01795-2018

M3 - Article (Academic Journal)

C2 - 30765504

VL - 53

JO - European Respiratory Journal

JF - European Respiratory Journal

SN - 0903-1936

IS - 4

M1 - 1801795

ER -