Umbilical cord blood DNA methylation in children who later develop type 1 diabetes,Diabetologia

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Umbilical cord blood DNA methylation in children who later develop type 1 diabetes
Diabetologia ( IF 8.4 ) Pub Date : 2022-06-18 , DOI: 10.1007/s00125-022-05726-1
Essi Laajala _{1,

2,

3,

4} , Ubaid Ullah Kalim _{1,

2} , Toni Grönroos _{1,

2} , Omid Rasool _{1,

2} , Viivi Halla-Aho ₄ , Mikko Konki ₁ , Roosa Kattelus _{1,

2} , Juha Mykkänen _{5,

6} , Mirja Nurmio ₇ , Mari Vähä-Mäkilä ₇ , Henna Kallionpää ₁ , Niina Lietzén ₁ , Bishwa R Ghimire ₈ , Asta Laiho _{1,

2} , Heikki Hyöty ₉ , Laura L Elo _{1,

2,

10} , Jorma Ilonen ₁₁ , Mikael Knip _{12,

13,

14} , Riikka J Lund ₁ , Matej Orešič _{1,

2,

15} , Riitta Veijola ₁₆ , Harri Lähdesmäki ₄ , Jorma Toppari _{6,

7,

17} , Riitta Lahesmaa _{1,

2,

10}

Affiliation

Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
InFLAMES Research Flagship Center, University of Turku, Turku, Finland.
Turku Doctoral Programme of Molecular Medicine, University of Turku, Turku, Finland.
Department of Computer Science, Aalto University, Espoo, Finland.
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Department of Virology, Faculty of Medicine and Biosciences, University of Tampere, Tampere, Finland.
Institute of Biomedicine, University of Turku, Turku, Finland.
Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Center for Child Health Research, Tampere University Hospital, Tampere, Finland.
School of Medical Sciences, Örebro University, Örebro, Sweden.
Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland.
Department of Pediatrics, Turku University Hospital, Turku, Finland.

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

中文翻译：

后来患 1 型糖尿病的儿童的脐带血 DNA 甲基化

目标/假设

最近在从幼儿身上采集的全血中观察到独特的 DNA 甲基化模式先于 1 型糖尿病发生。我们的目的是确定围产期 DNA 甲基化是否与后来进展为 1 型糖尿病有关。

方法

对芬兰 1 型糖尿病预测和预防 (DIPP) 研究中收集的脐带血样本进行了简化代表性亚硫酸氢盐测序 (RRBS) 分析。将后来诊断为 1 型糖尿病和/或多种胰岛自身抗体检测呈阳性的儿童 ( n = 43) 与对照个体 ( n = 79) 进行比较，对照个体在 DIPP 随访期间直至 15 岁仍保持自身抗体阴性。分析中包括与怀孕和母亲相关的潜在混杂因素。