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Genome-wide identification of DNA methylation QTLs in whole blood highlights pathways for cardiovascular disease. | LitMetric

AI Article Synopsis

  • - The study analyzes over 415,000 CpG methylation sites in more than 4,170 individuals to identify methylation quantitative trait loci (meQTLs) and explore their relationship with genetic variants linked to cardiovascular diseases (CVD) through genome-wide association studies (GWAS).
  • - Researchers mapped millions of meQTL variants, confirmed their findings in an independent cohort, and identified 92 potential causal CpGs for CVD traits using Mendelian randomization methods.
  • - The research also reveals connections between gene expression and methylation, including 22 trans-meQTL hotspots influencing the expression of nearby regulatory genes, contributing valuable insights into the role of DNA methylation in diseases.

Article Abstract

Identifying methylation quantitative trait loci (meQTLs) and integrating them with disease-associated variants from genome-wide association studies (GWAS) may illuminate functional mechanisms underlying genetic variant-disease associations. Here, we perform GWAS of >415 thousand CpG methylation sites in whole blood from 4170 individuals and map 4.7 million cis- and 630 thousand trans-meQTL variants targeting >120 thousand CpGs. Independent replication is performed in 1347 participants from two studies. By linking cis-meQTL variants with GWAS results for cardiovascular disease (CVD) traits, we identify 92 putatively causal CpGs for CVD traits by Mendelian randomization analysis. Further integrating gene expression data reveals evidence of cis CpG-transcript pairs causally linked to CVD. In addition, we identify 22 trans-meQTL hotspots each targeting more than 30 CpGs and find that trans-meQTL hotspots appear to act in cis on expression of nearby transcriptional regulatory genes. Our findings provide a powerful meQTL resource and shed light on DNA methylation involvement in human diseases.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753136PMC
http://dx.doi.org/10.1038/s41467-019-12228-zDOI Listing

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