Epigenome-Wide Association Study Reveals CpG Sites Associated with Thyroid Function and Regulatory Effects on KLF9

Antoine Weihs, Layal Chaker, Tiphaine C. Martin, Kim V.E. Braun, Purdey J. Campbell, Simon R. Cox, Myriam Fornage, Christian Gieger, Hans J. Grabe, Harald Grallert, Sarah E. Harris, Brigitte Kühnel, Riccardo E. Marioni, Nicholas G. Martin, Daniel L. McCartney, Allan F. McRae, Christa Meisinger, Joyce B.J. van Meurs, Jana Nano, Matthias NauckAnnette Peters, Holger Prokisch, Michael Roden, Elizabeth Selvin, Marian Beekman, Diana van Heemst, Eline P. Slagboom, Brenton R. Swenson, Adrienne Tin, Pei Chien Tsai, Andre Uitterlinden, W. Edward Visser, Henry Völzke, Melanie Waldenberger, John P. Walsh, Anna Köttgen, Scott G. Wilson, Robin P. Peeters, Jordana T. Bell, Marco Medici, Alexander Teumer

Research output: Contribution to journalArticlepeer-review

2 Citations (Web of Science)


Background: Thyroid hormones play a key role in differentiation and metabolism and are known regulators of gene expression through both genomic and epigenetic processes including DNA methylation. The aim of this study was to examine associations between thyroid hormones and DNA methylation. Methods: We carried out a fixed-effect meta-analysis of epigenome-wide association study (EWAS) of blood DNA methylation sites from 8 cohorts from the ThyroidOmics Consortium, incorporating up to 7073 participants of both European and African ancestry, implementing a discovery and replication stage. Statistical analyses were conducted using normalized beta CpG values as dependent and log-transformed thyrotropin (TSH), free thyroxine, and free triiodothyronine levels, respectively, as independent variable in a linear model. The replicated findings were correlated with gene expression levels in whole blood and tested for causal influence of TSH and free thyroxine by two-sample Mendelian randomization (MR). Results: Epigenome-wide significant associations (p-value
Original languageEnglish
Pages (from-to)301-311
Number of pages11
JournalThyroid : official journal of the American Thyroid Association
Issue number3
Publication statusPublished - 1 Mar 2023


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