The relevance of changes in DNAm intensity in whole blood to other tissues was tested by analysis of genome-wide DNAm data, generated using the Illumina Infinium Human Methylation 450K BeadChip array, from human liver, adipose tissue, and skeletal muscle, as previously published (26 (link)). Human liver DNAm data were from participants of the Kuopio Obesity Surgery Study (KOBS); 35 with T2DM and 60 without (27 (link)). Data on adipose tissue (14 pairs), skeletal muscle (17 pairs), and blood (19 pairs) were from monozygotic twins discordant for T2DM (26 (link),28 (link),29 (link)). Adipose tissue and skeletal muscle from the same individual were available for most of these twin pairs (16 pairs in blood/muscle and 14 pairs in blood/fat); concordance in DNAm intensity across these tissues was tested for each highlighted MVP by Spearman correlation tests. We further tested cross-tissue correlations in DNAm at T2DM-associated MVPs between blood and other tissues of relevance to T2DM etiology, liver, and pancreas in publicly available Infinium HumanMethylation450 BeadChip array data from six cadavers sampled within 12 h postmortem (mean [SD] age 65.5 [7.2] years) (30 (link)).
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Cross-tissue Validation of T2DM-associated DNA Methylation
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Corresponding Organization : University of Cambridge
Other organizations : Imperial College London, Agency for Science, Technology and Research, National University of Singapore, National Heart Lung and Blood Institute, National Institutes of Health, Boston University, Boston Children's Hospital, University College London, Queen Mary University of London, Massachusetts General Hospital, Harvard University, Broad Institute, Ealing Hospital, Imperial College Healthcare NHS Trust, University of Eastern Finland, Kuopio University Hospital, AstraZeneca (Sweden), Scania (Sweden), Lund University, Harvard Pilgrim Health Care, Nanyang Technological University
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Variable analysis
independent variables
- Presence or absence of Type 2 Diabetes Mellitus (T2DM)
- Genome-wide DNA methylation (DNAm) intensity in whole blood, liver, adipose tissue, and skeletal muscle
- Age of participants
- Time of postmortem sampling for liver, pancreas, and other tissues (within 12 hours)
- Positive control: Genome-wide DNAm data from human liver, adipose tissue, and skeletal muscle from previous studies
- Negative control: Not explicitly mentioned
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