Epigenetics (Dec 2024)
Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations
- Jessica I. Lundin,
- Ulrike Peters,
- Yao Hu,
- Farah Ammous,
- Christy L. Avery,
- Emelia J. Benjamin,
- Joshua C. Bis,
- Jennifer A. Brody,
- Chris Carlson,
- Mary Cushman,
- Chris Gignoux,
- Xiuqing Guo,
- Jeff Haessler,
- Chris Haiman,
- Roby Joehanes,
- Silva Kasela,
- Eimear Kenny,
- Tuuli Lapalainien,
- Daniel Levy,
- Chunyu Liu,
- Yongmei Liu,
- Ruth J.F. Loos,
- Ake Lu,
- Tara Matise,
- Kari E. North,
- Sungshim L. Park,
- Scott M. Ratliff,
- Alex Reiner,
- Stephen S. Rich,
- Jerome I. Rotter,
- Jennifer A. Smith,
- Nona Sotoodehnia,
- Russell Tracy,
- David Van den Berg,
- Huichun Xu,
- Ting Ye,
- Wei Zhao,
- Laura M. Raffield,
- Charles Kooperberg
Affiliations
- Jessica I. Lundin
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Ulrike Peters
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Yao Hu
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Farah Ammous
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA
- Christy L. Avery
- Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
- Emelia J. Benjamin
- Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston University School of Public Health, Boston, MA, USA
- Joshua C. Bis
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA
- Jennifer A. Brody
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA
- Chris Carlson
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Mary Cushman
- Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT, USA
- Chris Gignoux
- Interdisciplinary Quantitative Biology, University of Colorado, Boulder, CO, USA
- Xiuqing Guo
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA
- Jeff Haessler
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Chris Haiman
- Department of Environmental Medicine and Public Health, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Roby Joehanes
- Population Sciences Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, USA
- Silva Kasela
- New York Genome Center, New York, NY
- Eimear Kenny
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Tuuli Lapalainien
- New York Genome Center, New York, NY
- Daniel Levy
- Population Sciences Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, USA
- Chunyu Liu
- Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
- Yongmei Liu
- Duke Molecular Physiology Institute, Duke University, Durham, NC, USA
- Ruth J.F. Loos
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Ake Lu
- Department of Human Genetics, University of California LA, Los Angeles, CA, USA
- Tara Matise
- Department of Genetics, Rutgers University, New Brunswick, NJ, USA
- Kari E. North
- Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
- Sungshim L. Park
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA
- Scott M. Ratliff
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA
- Alex Reiner
- Department of Epidemiology, University of Washington, Seattle, WA, USA
- Stephen S. Rich
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
- Jerome I. Rotter
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA
- Jennifer A. Smith
- Department of Epidemiology, School of Public Health, and Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA
- Nona Sotoodehnia
- Cardiovascular Health Research Unit, Harborview Medical Center, Seattle, WA, USA
- Russell Tracy
- Department of Biochemistry, University of Vermont, Burlington, VT, USA
- David Van den Berg
- Department of Environmental Medicine and Public Health, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Huichun Xu
- Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
- Ting Ye
- Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA
- Wei Zhao
- Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA
- Laura M. Raffield
- Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
- Charles Kooperberg
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
- DOI
- https://doi.org/10.1080/15592294.2024.2333668
- Journal volume & issue
-
Vol. 19,
no. 1
Abstract
ABSTRACTSystemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory mechanisms to improve the understanding of chronic inflammation. The racially and ethnically diverse participants in this study were included as 50% White, 41% Black or African American, 7% Hispanic or Latino/a, and 2% Native Hawaiian, Asian American, American Indian, or Alaska Native (total n = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (CADM3, NALCN, NLRC5, ZNF792, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (p < 1.2E–7). The downstream pathways affected by DNA methylation included the identification of IFI16 and IRF7 CpG-gene transcript pairs which contributed to the innate immune response gene enrichment pathway along with NLRC5, NOD2, and AIM2. Gene enrichment analysis also identified the nuclear factor-kappaB transcription pathway. Using two-sample Mendelian randomization (MR) we inferred methylation at three CpG sites as causal for CRP levels using both White and Black or African American MR instrument variables. Overall, we identified novel CpG sites and gene transcripts that could be valuable in understanding the specific cellular processes and pathogenic mechanisms involved in inflammation.
Keywords
