Association of medically assisted reproduction with offspring cord blood DNA methylation across cohorts.
dc.contributor.author | Caramaschi, D | |
dc.contributor.author | Jungius, J | |
dc.contributor.author | Page, CM | |
dc.contributor.author | Novakovic, B | |
dc.contributor.author | Saffery, R | |
dc.contributor.author | Halliday, J | |
dc.contributor.author | Lewis, S | |
dc.contributor.author | Magnus, MC | |
dc.contributor.author | London, SJ | |
dc.contributor.author | Håberg, SE | |
dc.contributor.author | Relton, CL | |
dc.contributor.author | Lawlor, DA | |
dc.contributor.author | Elliott, HR | |
dc.date.accessioned | 2023-02-24T09:07:44Z | |
dc.date.issued | 2021-06-17 | |
dc.date.updated | 2023-02-23T16:51:49Z | |
dc.description.abstract | STUDY QUESTION: Is cord blood DNA methylation associated with having been conceived by medically assisted reproduction? SUMMARY ANSWER: This study does not provide strong evidence of an association of conception by medically assisted reproduction with variation in infant blood cell DNA methylation. WHAT IS KNOWN ALREADY: Medically assisted reproduction consists of procedures used to help infertile/subfertile couples conceive, including ART. Due to its importance in gene regulation during early development programming, DNA methylation and its perturbations associated with medically assisted reproduction could reveal new insights into the biological effects of assisted reproductive technologies and potential adverse offspring outcomes. STUDY DESIGN, SIZE, DURATION: We investigated the association of DNA methylation and medically assisted reproduction using a case-control study design (N = 205 medically assisted reproduction cases and N = 2439 naturally conceived controls in discovery cohorts; N = 149 ART cases and N = 58 non-ART controls in replication cohort). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: We assessed the association between medically assisted reproduction and DNA methylation at birth in cord blood (205 medically assisted conceptions and 2439 naturally conceived controls) at >450 000 CpG sites across the genome in two sub-samples of the UK Avon Longitudinal Study of Parents and Children (ALSPAC) and two sub-samples of the Norwegian Mother, Father and Child Cohort Study (MoBa) by meta-analysis. We explored replication of findings in the Australian Clinical review of the Health of adults conceived following Assisted Reproductive Technologies (CHART) study (N = 149 ART conceptions and N = 58 controls). MAIN RESULTS AND THE ROLE OF CHANCE: The ALSPAC and MoBa meta-analysis revealed evidence of association between conception by medically assisted reproduction and DNA methylation (false-discovery-rate-corrected P-value < 0.05) at five CpG sites which are annotated to two genes (percentage difference in methylation per CpG, cg24051276: Beta = 0.23 (95% CI 0.15,0.31); cg00012522: Beta = 0.47 (95% CI 0.31, 0.63); cg17855264: Beta = 0.31 (95% CI 0.20, 0.43); cg17132421: Beta = 0.30 (95% CI 0.18, 0.42); cg18529845: Beta = 0.41 (95% CI 0.25, 0.57)). Methylation at three of these sites has been previously linked to cancer, aging, HIV infection and neurological diseases. None of these associations replicated in the CHART cohort. There was evidence of a functional role of medically assisted reproduction-induced hypermethylation at CpG sites located within regulatory regions as shown by putative transcription factor binding and chromatin remodelling. LIMITATIONS, REASONS FOR CAUTIONS: While insufficient power is likely, heterogeneity in types of medically assisted reproduction procedures and between populations may also contribute. Larger studies might identify replicable variation in DNA methylation at birth due to medically assisted reproduction. WIDER IMPLICATIONS OF THE FINDINGS: Newborns conceived with medically assisted procedures present with divergent DNA methylation in cord blood white cells. If these associations are true and causal, they might have long-term consequences for offspring health. | en_GB |
dc.description.sponsorship | US National Institute of Health | en_GB |
dc.description.sponsorship | European Research Counci | en_GB |
dc.description.sponsorship | European Union’s Horizon 2020 | en_GB |
dc.description.sponsorship | NIHR Biomedical Centre at the University Hospitals Bristol NHS Foundation Trust | en_GB |
dc.description.sponsorship | University of Bristol | en_GB |
dc.format.extent | 2403-2413 | |
dc.format.medium | ||
dc.identifier.citation | Vol. 36, No. 8, pp. 2403-2413 | en_GB |
dc.identifier.doi | https://doi.org/10.1093/humrep/deab137 | |
dc.identifier.grantnumber | R01 DK10324 | en_GB |
dc.identifier.grantnumber | FP7/2007-2013 | en_GB |
dc.identifier.grantnumber | 733206 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/132532 | |
dc.identifier | ORCID: 0000-0002-9740-871X (Caramaschi, Doretta) | |
dc.identifier | ScopusID: 16021357200 (Caramaschi, Doretta) | |
dc.language.iso | en | en_GB |
dc.publisher | Oxford University Press | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/34136910 | en_GB |
dc.relation.url | https://www.fhi.no/en/studies/moba/for-forskere-artikler/research-and-data-access/ | en_GB |
dc.relation.url | http://www.bristol.ac.uk/alspac/researchers/access/ | en_GB |
dc.rights | © The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. | en_GB |
dc.subject | ALSPAC | en_GB |
dc.subject | CHART | en_GB |
dc.subject | DNA methylation | en_GB |
dc.subject | IVF | en_GB |
dc.subject | MoBa | en_GB |
dc.subject | assisted reproductive technology | en_GB |
dc.subject | epigenetics | en_GB |
dc.subject | medically assisted reproduction | en_GB |
dc.title | Association of medically assisted reproduction with offspring cord blood DNA methylation across cohorts. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-02-24T09:07:44Z | |
dc.identifier.issn | 0268-1161 | |
exeter.place-of-publication | England | |
dc.description | This is the final version. Available from Oxford University Press via the DOI in this record. | en_GB |
dc.description | Data availability: The data underlying this article cannot be shared publicly for the privacy of individuals that participated in the study. The data will be shared on reasonable request to the individual cohorts. For ALSPAC, data are available according to the procedures listed at http://www.bristol.ac.uk/alspac/researchers/access/. For MoBa, data can be requested at https://www.fhi.no/en/studies/moba/for-forskere-artikler/research-and-data-access/. | en_GB |
dc.identifier.eissn | 1460-2350 | |
dc.identifier.journal | Human Reproduction | en_GB |
dc.relation.ispartof | Hum Reprod, 36(8) | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2021-04-27 | |
dc.rights.license | CC BY | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2021-06-17 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-02-24T09:02:08Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2023-02-24T09:09:08Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2021-06-17 |
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