@article{322c5e72e2164dee96fa3f1afaf9f614,
title = "Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs",
abstract = "Background: Cord blood is a commonly used tissue in environmental, genetic, and epigenetic population studies due to its ready availability and potential to inform on a sensitive period of human development. However, the introduction of maternal blood during labor or cross-contamination during sample collection may complicate downstream analyses. After discovering maternal contamination of cord blood in a cohort study of 150 neonates using Illumina 450K DNA methylation (DNAm) data, we used a combination of linear regression and random forest machine learning to create a DNAm-based screening method. We identified a panel of DNAm sites that could discriminate between contaminated and non-contaminated samples, then designed pyrosequencing assays to pre-screen DNA prior to being assayed on an array. Results: Maternal contamination of cord blood was initially identified by unusual X chromosome DNA methylation patterns in 17 males. We utilized our DNAm panel to detect contaminated male samples and a proportional amount of female samples in the same cohort. We validated our DNAm screening method on an additional 189 sample cohort using both pyrosequencing and DNAm arrays, as well as 9 publically available cord blood 450K data sets. The rate of contamination varied from 0 to 10% within these studies, likely related to collection specific methods. Conclusions: Maternal blood can contaminate cord blood during sample collection at appreciable levels across multiple studies. We have identified a panel of markers that can be used to identify this contamination, either post hoc after DNAm arrays have been completed, or in advance using a targeted technique like pyrosequencing.",
keywords = "450K, Blood banking, Contamination, Cord blood, DNA methylation, Genotyping, Maternal blood",
author = "Morin, {Alexander M.} and Evan Gatev and McEwen, {Lisa M.} and Macisaac, {Julia L.} and Lin, {David T.S.} and Nastassja Koen and Darina Czamara and Katri R{\"a}ikk{\"o}nen and Zar, {Heather J.} and Karestan Koenen and Stein, {Dan J.} and Kobor, {Michael S.} and Jones, {Meaghan J.}",
note = "Funding Information: This work was supported by the National Institutes of Health (grant number R21HD085849 to KK); the AllerGen Network of Centers of Excellence (grant number GE-2 to MSK); the Bill and Melinda Gates Foundation (grant number OPP 1017641 to HJZ). Individual team members were supported by the National Research Foundation and the South African Medical Research Council (DJS and NK), and the Canadian Institute of Health Research (LMM). No funding agencies had any role in the design of the study and collection, analysis, interpretation of data or in writing the manuscript. Funding Information: We would like to thank Whitney Barnett for her assistance with this manuscript. We thank the Drakenstein study staff, the clinical and administrative staff of the Western Cape Government Health Department at Paarl Hospital and at the clinics for support of the study. We also thank our collaborators and the masters, doctoral, and postdoctoral students for their work on the study. Finally, we thank all mothers and children enrolled in the Drakenstein Child Health Study. The PREDO study would not have been possible without the dedicated contribution of the PREDO Study group members: Esa H{\"a}m{\"a}l{\"a}inen, Eero Kajantie, Jari Lahti, Hannele Laivuori, Anu-Katriina Pesonen, and Pia Villa. We also thank the PREDO study hospitals, and cohort mothers, fathers, and children for their enthusiastic participation. The PREDO study has received funding from the Academy of Finland, EraNet, EVO (a special state subsidy for health science research), University of Helsinki Research Funds, the Signe and Ane Gyllenberg foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Jane and Aatos Erkko Foundation, the Novo Nordisk Foundation, the P{\"a}ivikki and Sakari Sohlberg Foundation, and the Sigrid Juselius Foundation. Publisher Copyright: {\textcopyright} The Author(s). 2017.",
year = "2017",
month = jul,
day = "25",
doi = "10.1186/s13148-017-0370-2",
language = "English",
volume = "9",
journal = "Clinical Epigenetics",
issn = "1868-7075",
publisher = "BioMed Central Ltd.",
number = "1",
}