Epigenome-wide Association Study Shows Differential DNA Methylation of MDC1, KLF9, and CUTA in Autoimmune Thyroid Disease
Copyright policy )Epigenome-wide Association Study Shows Differential DNA Methylation of MDC1, KLF9, and CUTA in Autoimmune Thyroid Disease
Abstract Context Autoimmune thyroid disease (AITD) includes Graves disease (GD) and Hashimoto disease (HD), which often run in the same family. AITD etiology is incompletely understood: Genetic factors may account for up to 75% of phenotypic variance, whereas epigenetic effects (including DNA methylation [DNAm]) may contribute to the remaining variance (eg, why some individuals develop GD and others HD). Objective This work aimed to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) comparing GD to HD. Methods Whole-blood DNAm was measured across the genome using the Infinium MethylationEPIC array in 32 Australian patients with GD and 30 with HD (discovery cohort) and 32 Danish patients with GD and 32 with HD (replication cohort). Linear mixed models were used to test for differences in quantile-normalized β values of DNAm between GD and HD and data were later meta-analyzed. Comb-p software was used to identify DMRs. Results We identified epigenome-wide significant differences (P < 9E-8) and replicated (P < .05) 2 DMPs between GD and HD (cg06315208 within MDC1 and cg00049440 within KLF9). We identified and replicated a DMR within CUTA (5 CpGs at 6p21.32). We also identified 64 DMPs and 137 DMRs in the meta-analysis. Conclusion Our study reveals differences in DNAm between GD and HD, which may help explain why some people develop GD and others HD and provide a link to environmental risk factors. Additional research is needed to advance understanding of the role of DNAm in AITD and investigate its prognostic and therapeutic potential.
- University of Western Australia Australia
- University of Southern Denmark Denmark
- University of Leicester United Kingdom
- Sir Charles Gairdner Hospital Australia
- King's College London United Kingdom
Cell Cycle Proteins/genetics, Clinical Research Article, DNA methylation, Hashimoto disease, Signal Transducing/genetics, epigenome, Australia/epidemiology, Australia, Kruppel-Like Transcription Factors, Adaptor Proteins, Cell Cycle Proteins, Hashimoto Disease, DNA Methylation, Graves Disease, Epigenesis, Genetic, Hashimoto Disease/genetics, Epigenome, Genetic, Graves disease, Graves Disease/genetics, Humans, Kruppel-Like Transcription Factors/genetics, Epigenesis, Adaptor Proteins, Signal Transducing
Cell Cycle Proteins/genetics, Clinical Research Article, DNA methylation, Hashimoto disease, Signal Transducing/genetics, epigenome, Australia/epidemiology, Australia, Kruppel-Like Transcription Factors, Adaptor Proteins, Cell Cycle Proteins, Hashimoto Disease, DNA Methylation, Graves Disease, Epigenesis, Genetic, Hashimoto Disease/genetics, Epigenome, Genetic, Graves disease, Graves Disease/genetics, Humans, Kruppel-Like Transcription Factors/genetics, Epigenesis, Adaptor Proteins, Signal Transducing
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