| Title: |
Expression quantitative trait methylation analysis elucidates gene regulatory effects of DNA methylation: the Framingham Heart Study |
| 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 |
| Contributors: |
Ophthalmology and Visual Sciences; Medicine |
| Source: |
Scientific reports ; 13 ; 1 ; 12952 ; England |
| Publication Year: |
2025 |
| Collection: |
University of Massachusetts, Medical School: eScholarship@UMMS |
| Subject Terms: |
Epigenetics; Transcriptomics |
| Description: |
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. ; No embargo |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Scientific Reports; https://doi.org/10.1038/s41598-023-39936-3; https://hdl.handle.net/20.500.14038/54433 |
| DOI: |
10.1038/s41598-023-39936-3 |
| Availability: |
https://doi.org/10.1038/s41598-023-39936-3; https://hdl.handle.net/20.500.14038/54433 |
| Rights: |
Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons. org/ licenses/ by/4. 0/. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.646A74FD |
| Database: |
BASE |