2017
Disease variants alter transcription factor levels and methylation of their binding sites
Publication
Publication
Nature Genetics , Volume 49 - Issue 1 p. 131- 138
Most disease-associated genetic variants are noncoding, making it challenging to design experiments to understand their functional consequences. Identification of expression quantitative trait loci (eQTLs) has been a powerful approach to infer the downstream effects of disease-associated variants, but most of these variants remain unexplained. The analysis of DNA methylation, a key component of the epigenome, offers highly complementary data on the regulatory potential of genomic regions. Here we show that disease-associated variants have widespread effects on DNA methylation in trans that likely reflect differential occupancy of trans binding sites by cis-regulated transcription factors. Using multiple omics data sets from 3,841 Dutch individuals, we identified 1,907 established trait-associated SNPs that affect the methylation levels of 10,141 different CpG sites in trans (false discovery rate (FDR) < 0.05). These included SNPs that affect both the expression of a nearby transcription factor (such as NFKB1, CTCF and NKX2-3) and methylation of its respective binding site across the genome. Trans methylation QTLs effectively expose the downstream effects of disease-associated variants.
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| doi.org/10.1038/ng.3721, hdl.handle.net/1765/108215 | |
| Nature Genetics | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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Bonder, M., Luijk, R., Zhernakova, D.V. (Daria V), Moed, H., Deelen, P., Vermaat, M., … Heijmans, B.T. (Bastiaan T.). (2017). Disease variants alter transcription factor levels and methylation of their binding sites. Nature Genetics, 49(1), 131–138. doi:10.1038/ng.3721 |
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