Epigenome-Wide Association Study Reveals CpG Sites Associated with Thyroid Function and Regulatory Effects on KLF9
Authors' conclusion
We report novel associations between TSH, thyroid hormones, and blood-based DNA methylation.
Study context
- Population
- Participants of European and African ancestry from 8 cohorts of the ThyroidOmics Consortium; blood DNA methylationup to
- Participants
- 7,073 participants
- Outcome
- Associations of blood DNA methylation (CpG sites) with log-transformed TSH, free thyroxine and free triiodothyronine
Methodological detailsfixed-effect meta-analysis, discovery and replication stage, two-sample Mendelian randomization, 8 cohorts (ThyroidOmics Consortium)
- Fixed-effect meta-analysis
- Discovery and replication stage
- Two-sample Mendelian randomization
- 8 cohorts (ThyroidOmics Consortium)
Pooled result
As reported in the abstract
Epigenome-wide significant CpG associations (p-value <1.1E-7), discovered and replicated
CpGs associated with free thyroxine
3
CpGs associated with free triiodothyronine
5
CpGs associated with TSH
2
Combined p-values
1.5E-9 to 4.3E-28
Further pooled results
Mendelian randomization and gene expression
- Mendelian randomization (MR) supported a causal effect of thyroid status on DNA methylation of KLF9
- Methylation of cg00049440 in KLF9 inversely correlated with KLF9 expression in blood
- CpG at CSNK1D/LINC01970 overlapped with thyroid hormone receptor alpha binding peaks in liver cells
Heritability and methylation QTLs
- Total additive heritability of methylation of the six significant CpGs
- between 25% and 57%
- Significant methylation QTLs for CpGs at KLF9, FKBP5, LRRC8D and CSNK1D/LINC01970
Original publication
Epigenome-Wide Association Study Reveals CpG Sites Associated with Thyroid Function and Regulatory Effects on KLF9. Thyroid. Published 1 March 2023. doi:10.
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