Expression quantitative trait methylation analysis elucidates gene regulatory effects of DNA methylation: the Framingham Heart Study

Expression quantitative trait methylation (eQTM) analysis identifies DNA CpG sites at which methylation is associated with gene expression. The present study describes an eQTM resource of CpG-transcript pairs derived from whole blood DNA methylation and RNA sequencing gene expression data in 2115 Fr...

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Published in:Scientific reports Vol. 13; no. 1; pp. 12952 - 11
Main Authors: Keshawarz, Amena, Bui, Helena, Joehanes, Roby, Ma, Jiantao, Liu, Chunyu, Huan, Tianxiao, Hwang, Shih-Jen, Tejada, Brandon, Sooda, Meera, Courchesne, Paul, Munson, Peter J., Demirkale, Cumhur Y., Yao, Chen, Heard-Costa, Nancy L., Pitsillides, Achilleas N., Lin, Honghuang, Liu, Ching-Ti, Wang, Yuxuan, Peloso, Gina M., Lundin, Jessica, Haessler, Jeffrey, Du, Zhaohui, Cho, Michael, Hersh, Craig P., Castaldi, Peter, Raffield, Laura M., Wen, Jia, Li, Yun, Reiner, Alexander P., Feolo, Mike, Sharopova, Nataliya, Vasan, Ramachandran S., DeMeo, Dawn L., Carson, April P., Kooperberg, Charles, Levy, Daniel
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 10.08.2023
Nature Publishing Group
Nature Portfolio
Subjects:
631/337/176
631/337/2019
Blood
Cardiovascular Diseases - genetics
Cell signaling
CpG islands
CpG Islands - genetics
Deoxyribonucleic acid
DNA
DNA Methylation
DNA sequencing
Female
Gene expression
Gene Expression Regulation
Genome-Wide Association Study
Health promotion
Heart
Humanities and Social Sciences
Humans
Immune response
Longitudinal Studies
multidisciplinary
Quantitative Trait Loci
Science
Science (multidisciplinary)
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:Expression quantitative trait methylation (eQTM) analysis identifies DNA CpG sites at which methylation is associated with gene expression. The present study describes an eQTM resource of CpG-transcript pairs derived from whole blood DNA methylation and RNA sequencing gene expression data in 2115 Framingham Heart Study participants. We identified 70,047 significant cis CpG-transcript pairs at p  < 1E−7 where the top most significant eGenes (i.e., gene transcripts associated with a CpG) were enriched in biological pathways related to cell signaling, and for 1208 clinical traits (enrichment false discovery rate [FDR] ≤ 0.05). We also identified 246,667 significant trans CpG-transcript pairs at p  < 1E−14 where the top most significant eGenes were enriched in biological pathways related to activation of the immune response, and for 1191 clinical traits (enrichment FDR ≤ 0.05). Independent and external replication of the top 1000 significant cis and trans CpG-transcript pairs was completed in the Women’s Health Initiative and Jackson Heart Study cohorts. Using significant cis CpG-transcript pairs, we identified significant mediation of the association between CpG sites and cardiometabolic traits through gene expression and identified shared genetic regulation between CpGs and transcripts associated with cardiometabolic traits. In conclusion, we developed a robust and powerful resource of whole blood eQTM CpG-transcript pairs that can help inform future functional studies that seek to understand the molecular basis of disease.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-39936-3