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DNA methylation differences at birth after conception through assisted reproductive technologies

medRxiv

Abstract

Summary The possible health consequences of assisted reproductive technology (ART) are a topic of intense study. Epigenetic mechanisms, such as changes in DNA methylation (DNAm), come forward from animal studies as a potential mechanism linking ART and health. Here we report on an epigenome-wide association study (EWAS) of DNAm in cord blood of 87 infants conceived with in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI) and 70 who were not. We found no difference in global methylation levels, but identified nineteen CpG dinucleotides (CpGs) associated with ART (effect estimates: 0.5-4.9%). There was no difference between IVF and ICSI and the CpGs map to genes related to brain function/development or the plethora of conditions linked to subfertility. Functional annotation did not point to likely functional consequences. Concluding, ART is associated with DNA methylation differences in cord blood, but these differences are limited in number, effect size and with unknown functional consequences.

Authors 11

  1. Leiden University Medical Center · Erasmus MC

    Affiliation as printed

    Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center

    Periconceptional Epidemiology, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center Rotterdam

    Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 300RC Leiden, The Netherlands

    Periconceptional Epidemiology, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 50, 305GE Rotterdam, The Netherlands

  2. Karolinska Institutet

    Affiliation as printed

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet

    Pediatric Allergy and Pulmonology Unit, Astrid Lindgren Children’s Hospital

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden

    Pediatric Allergy and Pulmonology Unit, Astrid Lindgren Children's Hospital, 171 76 Stockholm, Sweden

  3. Danderyds sjukhus · Karolinska Institutet

    Affiliation as printed

    Department of Clinical Sciences, Danderyd hospital, Karolinska Institutet

    Department of Clinical Sciences, Danderyd hospital, Karolinska Institutet 182 88 Stockholm Sweden

  4. Danderyds sjukhus · Karolinska Institutet

    Affiliation as printed

    Department of Clinical Sciences, Danderyd hospital, Karolinska Institutet

    Department of Clinical Sciences, Danderyd hospital, Karolinska Institutet 182 88 Stockholm Sweden

  5. Uppsala University · Carl von Linné Clinic

    Affiliation as printed

    Carl von Linné Clinic

    Center for Reproductive Biology in Uppsala, University of Agricultural Sciences and Uppsala University

    Department of Women’s and Children’s Health, Uppsala University

    Carl von Linné Clinic, Uppsala, Sweden

    Center for Reproductive Biology in Uppsala, University of Agricultural Sciences and Uppsala University, Uppsala, Sweden

    Department of Women's and Children's Health, Uppsala University, 51 85 Uppsala, Sweden

  6. Karolinska Institutet

    Affiliation as printed

    Department of Women’s and Children’s Health, Karolinska Institutet

    Department of Women's and Children's Health, Karolinska Institutet, 171 77 Stockholm, Sweden

  7. Saint Göran Hospital

    Affiliation as printed

    Livio Fertilitetscentrum Kungsholmen

    Livio Fertilitetscentrum Kungsholmen, S:t Görans Sjukhus, 112 81 Stockholm, Sweden

  8. Fertilitetscentrum

    Affiliation as printed

    Livio Fertilitetscentrum Gärdet Storängsvägen

    Livio Fertilitetscentrum Gärdet Storängsvägen 10, 5 42 Stockholm

  9. Karolinska Institutet

    Affiliation as printed

    Institute of Environmental Medicine, Karolinska Institutet

    Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden

  10. Leiden University Medical Center

    Affiliation as printed

    Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center

    Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 300RC Leiden, The Netherlands

  11. Karolinska Institutet

    Affiliation as printed

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden

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References 63