Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations

Systemic 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 <i>n</i> = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (<i>CADM3</i>, <i>NALCN, NLRC5, ZNF792</i>, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (<i>p</i> &lt; 1.2E-7). The downstream pathways affected by DNA methylation included the identification of <i>IFI16</i> and <i>IRF7</i> CpG-gene transcript pairs which contributed to the innate immune response gene enrichment pathway along with <i>NLRC5</i>, <i>NOD2</i>, and <i>AIM2</i>. 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.

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UNC Libraries
Published
2024-11-06
DOI
https://doi.org/10.17615/b6xd-h115
Primary Topic
Dietary Effects on Health
Type
article
Field-Weighted Citation Impact
0.00

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article

Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations

Charles Kooperberg, Ruth J. F. Loos, Jessica I. Lundin, Mary Cushman et al.
UNC Libraries
Dietary Effects on Health
article

Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations

Charles Kooperberg, Ruth J. F. Loos, Jessica I. Lundin, Mary Cushman, Yao Hu, Jerome I. Rotter, Laura M. Raffield, Christy L. Avery, Farah Ammous, Huichun Xu, Eimear E. Kenny, Russell P. Tracy, Roby Joehanes, Ulrike Peters, Scott M. Ratliff, Tara C. Matise, Jennifer A. Smith, Kari E. North, Joshua C. Bis, Ake T. Lu, Emelia J. Benjamin, Jennifer A. Brody, Stephen S. Rich, Silva Kasela, Daniel A Levy, Sungshim L. Park, Alex P. Reiner, Wei Zhao, David Van Den Berg, Xiuqing Guo, Chunyu Liu, Ting Ye, Yongmei Liu, Nona Sotoodehnia, Tuuli Lapalainien, Chris Gignoux, Chris Carlson, Jeff Haessler, Chris Haiman, On Behalf of the PAGE Study
article en

Abstract

Systemic 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 <i>n</i> = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (<i>CADM3</i>, <i>NALCN, NLRC5, ZNF792</i>, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (<i>p</i> &lt; 1.2E-7). The downstream pathways affected by DNA methylation included the identification of <i>IFI16</i> and <i>IRF7</i> CpG-gene transcript pairs which contributed to the innate immune response gene enrichment pathway along with <i>NLRC5</i>, <i>NOD2</i>, and <i>AIM2</i>. 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.

UNC Libraries
University of North Carolina at Chapel Hill (US)
U.S. Department of Health and Human Services, Fred Hutchinson Cancer Research Center, Jackson State University, Broad Institute, Mississippi State Department of Health, Ministerio de Economía y Competitividad, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
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