Genome-wide association study

Differentially methylated regions

Genotype

Gene expression

CTCF

Biology

Promoter

Gene

Single-nucleotide polymorphism

Expression quantitative trait loci

DNA methylation

Genetics

Transcription factor

Computational biology

Methylation

CpG site

Quantitative trait locus

Enhancer

DNA binding site

Nature Genetics

Peter 't Hoen, Lude Franke, Bastiaan Heijmans and colleagues present a combined analysis of methylome and transcriptome data from a large collection of whole-blood samples to infer the downstream effects of disease-associated variants. They identify a large number of trait-associated SNPs influencing methylation of CpG sites in trans, providing insights into the downstream functional effects of many disease-associated variants. Most disease-associated genetic variants are noncoding, making it challenging to design experiments to understand their functional consequences1,2. 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 unexplained3,4. The analysis of DNA methylation, a key component of the epigenome5,6, offers highly complementary data on the regulatory potential of genomic regions7,8. Here we show that disease-associated variants have widespread effects on DNA methylati...

Disease variants alter transcription factor levels and methylation of their binding sites