@article{99db6f42d7e2409da579bf600ab1d11e,
title = "Umbilical cord blood DNA methylation in children who later develop type 1 diabetes",
abstract = "Aims/hypothesis: Distinct DNA methylation patterns have recently been observed to precede type 1 diabetes in whole blood collected from young children. Our aim was to determine whether perinatal DNA methylation is associated with later progression to type 1 diabetes. Methods: Reduced representation bisulphite sequencing (RRBS) analysis was performed on umbilical cord blood samples collected within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study. Children later diagnosed with type 1 diabetes and/or who tested positive for multiple islet autoantibodies (n = 43) were compared with control individuals (n = 79) who remained autoantibody-negative throughout the DIPP follow-up until 15 years of age. Potential confounding factors related to the pregnancy and the mother were included in the analysis. Results: No differences in the umbilical cord blood methylation patterns were observed between the cases and controls at a false discovery rate <0.05. Conclusions/interpretation: Based on our results, differences between children who progress to type 1 diabetes and those who remain healthy throughout childhood are not yet present in the perinatal DNA methylome. However, we cannot exclude the possibility that such differences would be found in a larger dataset. Graphical abstract: [Figure not available: see fulltext.].",
keywords = "Bisulphite sequencing, DNA methylation, Epigenomics, Follow-up study, Type 1 diabetes, Umbilical cord blood",
author = "Essi Laajala and Kalim, {Ubaid Ullah} and Toni Gr{\"o}nroos and Omid Rasool and Viivi Halla-aho and Mikko Konki and Roosa Kattelus and Juha Mykk{\"a}nen and Mirja Nurmio and Mari V{\"a}h{\"a}-M{\"a}kil{\"a} and Henna Kallionp{\"a}{\"a} and Niina Lietz{\'e}n and Ghimire, {Bishwa R.} and Asta Laiho and Heikki Hy{\"o}ty and Elo, {Laura L.} and Jorma Ilonen and Mikael Knip and Lund, {Riikka J.} and Matej Ore{\v s}i{\v c} and Riitta Veijola and Harri L{\"a}hdesm{\"a}ki and Jorma Toppari and Riitta Lahesmaa",
note = "Funding Information: We are grateful to the families for their participation in the DIPP Study, and the personnel of Turku University Hospital for their excellent collaboration, work with the families, and collection of the samples for the study. We also thank the personnel of the HLA laboratory at the University of Turku and the personnel of the islet autoantibody laboratory at the University of Oulu. We thank Emeritus Professor O. Simell (University of Turku, Finland) for his long-term commitment to the DIPP Study. We thank M. Hakkarainen (University of Turku, Finland) and S. Heinonen (University of Turku, Finland) for their excellent technical help. We acknowledge the Turku Bioscience Centre{\textquoteright}s core facility, the Finnish Functional Genomics Centre, supported by Biocenter Finland, for their assistance. We also acknowledge the Finnish Centre for Scientific Computing (CSC) and the computational resources provided by the Aalto Science-IT project. The graphical abstract was created with BioRender.com. The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. EL analysed the data, participated in interpretation of the results, prepared the figures and tables, and wrote the manuscript. UUK participated in interpretation of the results and drafting of the manuscript. TG was responsible for the technical validations by targeted pyrosequencing. OR supervised the laboratory experiments and participated in the design of the study setup. VH, BRG and AL participated in the data analysis. MKo and RK participated in the technical validations by targeted pyrosequencing. JM, MN and MV-M provided the clinical information on the study participants compiled by EL, HK and NL. HH, JI, MKn, RV and JT were responsible for the DIPP Study. LLE contributed to data analysis and interpretation and supervised BRG and AL. JI provided the samples and was responsible for the DNA isolation and HLA screening of the study participants. MKn and MO initiated and designed the study together with RL. RJL supervised MKo, was responsible for the bisulphite sequencing, and participated in interpretation of the results. RV directed the clinical multicentre DIPP Study, and was responsible for the DIPP autoantibody laboratory. HL supervised EL and VH for performance of data analysis, and participated in interpretation of the results. JT supervised MV-M and MN, and provided the clinical information on the study participants. RL initiated the study, designed the study setup, supervised the study, participated in interpretation of the results, and revised the manuscript. All authors contributed to the final version of the manuscript and approved its publication. RL is the guarantor of this work, and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
doi = "10.1007/s00125-022-05726-1",
language = "English",
volume = "65",
pages = "1534–1540",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "9",
}
