Expression quantitative trait methylation analysis elucidates gene regulatory effects of DNA methylation: the Framingham Heart Study
Year: 2023
Type: article
Abstract: 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.
Source: Scientific Reports
Authors: Amena Keshawarz, Helena Bui, Roby Joehanes, Jiantao Ma, Chunyu Liu, Tianxiao Huan, Shih-Jen Hwang, Brandon Tejada, Meera Sooda, Paul Courchesne, Peter J. Munson, Cumhur Y. Demirkale, Chen Yao, Nancy L. Heard-Costa, Achilleas N. Pitsillides, Honghuan Lin, Ching-Ti Liu, Yuxuan Wang, Gina M. Peloso, Jessica Lundin, Jeffrey Haessler, Zhaohui Du, Michael Cho, Craig P. Hersh, Peter Castaldi, Laura M. Raffield, Jia Wen, Yun Li, Alexander P. Reiner, Mike Feolo, Nataliya Sharopova, Ramachandran S. Vasan, Edwin K. Silverman, Dawn L. DeMeo, April P. Carson, Charles Kooperberg, Daniel Levy
Institutions: National Institutes of Health, National Heart, Lung, and Blood Institute, Framingham Heart Study, National Heart, Lung, and Blood Institute Division of Intramural Research, Tufts University, Boston University, University of Massachusetts Chan Medical School, Center for Information Technology, Fred Hutch Cancer Center, Brigham and Women's Hospital, Harvard University, University of North Carolina at Chapel Hill, University of Washington, National Center for Biotechnology Information, University of Mississippi Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,390
Funders: U.S. Department of Health and Human Services, Women's Health Initiative, Brigham and Women's Hospital, Ohio State University, Jackson State University, Wake Forest University, School of Medicine, Boston University, University of Pittsburgh, University of Nevada, Reno, MedStar Health Research Institute, Evans Medical Foundation, Mississippi State Department of Health, National Institutes of Health, University at Buffalo, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Environmental Health Sciences, National Institute on Minority Health and Health Disparities, NHLBI Division of Intramural Research
Awards: G1052645489, G1093951984, G1211708387, G1295889178, G1540916838, G1711244518, G1730507467, G1735617348, G1851406594, G2096685756, Rare variants and NHLBI traits in deeply phenotyped cohorts, G2221742881, G2281899837, G2316258288, G232264632, G2415573643, G265762973, G278200998, G2809357584, G2816736420, G3057025668, G3078883119, G3194560040, G3256118428, G3405256882, G350245564, G3819938352, G3827278403, Rare variants and NHLBI traits in deeply phenotyped cohorts, G4122490874, G4499735890, G4514711904, G4711807797, G47192932, G472208673, Genetic Studies of Blood Cell Traits in Multi-Ethnic Cohorts, G4897018079, G4976486911, G5042794962, G5164707915, G5478822001, G554960330, G5717342023, G571830633, G5777902738, G579045871, G5805320778, G6156766399, G6238440229, G631129105, G6374953548, G6571475356, G661039301, G6615318374, THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195, G6894818919, G7032370290, G7056032889, G7091571603, G7159829730, G7348868804, G7526106616, G7821233859, G7945866738, G796413602, G833338434, Studies of Rare Genetic Variation in the Isolated Population of Sardinia, G8566225511, G8615730155, G8683204365, G87163782, G8836210513, G89699440, G9000135092, Immune Cells in Alzheimer’s Disease and Related Dementias in the Jackson Heart Study, IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVAL, Biostatistics for Research in Environmental Health
OpenAlex ID: W4385723965