Altered DNA methylation in children born to mothers with rheumatoid arthritis during pregnancy

Hilal Ince-Askan, Pooja R Mandaviya, Janine F Felix, Liesbeth Duijts, Joyce B van Meurs, Johanna M W Hazes, Radboud J E M Dolhain

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVES: The main objective of this study was to determine whether the DNA methylation profile of children born to mothers with rheumatoid arthritis (RA) is different from that of children born to mothers from the general population. In addition, we aimed to determine whether any differences in methylation are associated with maternal RA disease activity or medication use during pregnancy.

METHODS: For this study, genome-wide DNA methylation was measured at cytosine-phosphate-guanine (CpG) sites, using the Infinium Illumina HumanMethylation 450K BeadChip, in 80 blood samples from children (mean age=6.8 years) born to mothers with RA. As controls, blood samples from 354 children (mean age=6.0 years) from the population-based Generation R Study were used. Linear mixed models were performed to investigate differential methylation between the groups, corrected for relevant confounders.

RESULTS: A total of 147 CpGs were differentially methylated between blood samples of children born to mothers with RA and the control blood samples. The five most significantly associated CpGs were cg06642177, cg08867893, cg06778273, cg07786668 and cg20116574. The differences in methylation were not associated with maternal RA disease activity or medication use during pregnancy.

CONCLUSIONS: DNA methylation at 147 CpGs differed between children born to mothers with RA and children born to mothers from the general population. It remains unknown whether the identified associations are causal, and if so whether they are caused by the disease or treatment. More research, including replication of these results, is necessary in order to strengthen the relevance of our findings for the later-life health of children born to mothers with RA.

Original languageEnglish
Pages (from-to)1198-1204
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume78
Issue number9
Early online date29 May 2019
DOIs
Publication statusPublished - Sep 2019

Keywords

  • ATRIAL-FIBRILLATION
  • DEHYDROGENASE
  • DISEASE-ACTIVITY
  • FAMINE
  • FETAL
  • GLUT12
  • GROWTH
  • MATERNAL SMOKING
  • PRENATAL EXPOSURE
  • ZFHX3 GENE

Cite this

Ince-Askan, H., Mandaviya, P. R., Felix, J. F., Duijts, L., van Meurs, J. B., Hazes, J. M. W., & Dolhain, R. J. E. M. (2019). Altered DNA methylation in children born to mothers with rheumatoid arthritis during pregnancy. Annals of the Rheumatic Diseases, 78(9), 1198-1204. https://doi.org/10.1136/annrheumdis-2018-214930
Ince-Askan, Hilal ; Mandaviya, Pooja R ; Felix, Janine F ; Duijts, Liesbeth ; van Meurs, Joyce B ; Hazes, Johanna M W ; Dolhain, Radboud J E M. / Altered DNA methylation in children born to mothers with rheumatoid arthritis during pregnancy. In: Annals of the Rheumatic Diseases. 2019 ; Vol. 78, No. 9. pp. 1198-1204.
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title = "Altered DNA methylation in children born to mothers with rheumatoid arthritis during pregnancy",
abstract = "OBJECTIVES: The main objective of this study was to determine whether the DNA methylation profile of children born to mothers with rheumatoid arthritis (RA) is different from that of children born to mothers from the general population. In addition, we aimed to determine whether any differences in methylation are associated with maternal RA disease activity or medication use during pregnancy.METHODS: For this study, genome-wide DNA methylation was measured at cytosine-phosphate-guanine (CpG) sites, using the Infinium Illumina HumanMethylation 450K BeadChip, in 80 blood samples from children (mean age=6.8 years) born to mothers with RA. As controls, blood samples from 354 children (mean age=6.0 years) from the population-based Generation R Study were used. Linear mixed models were performed to investigate differential methylation between the groups, corrected for relevant confounders.RESULTS: A total of 147 CpGs were differentially methylated between blood samples of children born to mothers with RA and the control blood samples. The five most significantly associated CpGs were cg06642177, cg08867893, cg06778273, cg07786668 and cg20116574. The differences in methylation were not associated with maternal RA disease activity or medication use during pregnancy.CONCLUSIONS: DNA methylation at 147 CpGs differed between children born to mothers with RA and children born to mothers from the general population. It remains unknown whether the identified associations are causal, and if so whether they are caused by the disease or treatment. More research, including replication of these results, is necessary in order to strengthen the relevance of our findings for the later-life health of children born to mothers with RA.",
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author = "Hilal Ince-Askan and Mandaviya, {Pooja R} and Felix, {Janine F} and Liesbeth Duijts and {van Meurs}, {Joyce B} and Hazes, {Johanna M W} and Dolhain, {Radboud J E M}",
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Altered DNA methylation in children born to mothers with rheumatoid arthritis during pregnancy. / Ince-Askan, Hilal; Mandaviya, Pooja R; Felix, Janine F; Duijts, Liesbeth; van Meurs, Joyce B; Hazes, Johanna M W; Dolhain, Radboud J E M.

In: Annals of the Rheumatic Diseases, Vol. 78, No. 9, 09.2019, p. 1198-1204.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Altered DNA methylation in children born to mothers with rheumatoid arthritis during pregnancy

AU - Ince-Askan, Hilal

AU - Mandaviya, Pooja R

AU - Felix, Janine F

AU - Duijts, Liesbeth

AU - van Meurs, Joyce B

AU - Hazes, Johanna M W

AU - Dolhain, Radboud J E M

N1 - © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2019/9

Y1 - 2019/9

N2 - OBJECTIVES: The main objective of this study was to determine whether the DNA methylation profile of children born to mothers with rheumatoid arthritis (RA) is different from that of children born to mothers from the general population. In addition, we aimed to determine whether any differences in methylation are associated with maternal RA disease activity or medication use during pregnancy.METHODS: For this study, genome-wide DNA methylation was measured at cytosine-phosphate-guanine (CpG) sites, using the Infinium Illumina HumanMethylation 450K BeadChip, in 80 blood samples from children (mean age=6.8 years) born to mothers with RA. As controls, blood samples from 354 children (mean age=6.0 years) from the population-based Generation R Study were used. Linear mixed models were performed to investigate differential methylation between the groups, corrected for relevant confounders.RESULTS: A total of 147 CpGs were differentially methylated between blood samples of children born to mothers with RA and the control blood samples. The five most significantly associated CpGs were cg06642177, cg08867893, cg06778273, cg07786668 and cg20116574. The differences in methylation were not associated with maternal RA disease activity or medication use during pregnancy.CONCLUSIONS: DNA methylation at 147 CpGs differed between children born to mothers with RA and children born to mothers from the general population. It remains unknown whether the identified associations are causal, and if so whether they are caused by the disease or treatment. More research, including replication of these results, is necessary in order to strengthen the relevance of our findings for the later-life health of children born to mothers with RA.

AB - OBJECTIVES: The main objective of this study was to determine whether the DNA methylation profile of children born to mothers with rheumatoid arthritis (RA) is different from that of children born to mothers from the general population. In addition, we aimed to determine whether any differences in methylation are associated with maternal RA disease activity or medication use during pregnancy.METHODS: For this study, genome-wide DNA methylation was measured at cytosine-phosphate-guanine (CpG) sites, using the Infinium Illumina HumanMethylation 450K BeadChip, in 80 blood samples from children (mean age=6.8 years) born to mothers with RA. As controls, blood samples from 354 children (mean age=6.0 years) from the population-based Generation R Study were used. Linear mixed models were performed to investigate differential methylation between the groups, corrected for relevant confounders.RESULTS: A total of 147 CpGs were differentially methylated between blood samples of children born to mothers with RA and the control blood samples. The five most significantly associated CpGs were cg06642177, cg08867893, cg06778273, cg07786668 and cg20116574. The differences in methylation were not associated with maternal RA disease activity or medication use during pregnancy.CONCLUSIONS: DNA methylation at 147 CpGs differed between children born to mothers with RA and children born to mothers from the general population. It remains unknown whether the identified associations are causal, and if so whether they are caused by the disease or treatment. More research, including replication of these results, is necessary in order to strengthen the relevance of our findings for the later-life health of children born to mothers with RA.

KW - ATRIAL-FIBRILLATION

KW - DEHYDROGENASE

KW - DISEASE-ACTIVITY

KW - FAMINE

KW - FETAL

KW - GLUT12

KW - GROWTH

KW - MATERNAL SMOKING

KW - PRENATAL EXPOSURE

KW - ZFHX3 GENE

U2 - 10.1136/annrheumdis-2018-214930

DO - 10.1136/annrheumdis-2018-214930

M3 - Article

C2 - 31142478

VL - 78

SP - 1198

EP - 1204

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 9

ER -