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 wh...
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| Veröffentlicht in: | Epigenetics 2024-12, Vol.19 (1), p.2333668 |
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| creator | Lundin, Jessica I. Peters, Ulrike Hu, Yao Ammous, Farah Avery, Christy L. Benjamin, Emelia J. Bis, Joshua C. Brody, Jennifer A. Carlson, Chris Cushman, Mary Gignoux, Chris Guo, Xiuqing Haessler, Jeff Haiman, Chris Joehanes, Roby Kasela, Silva Kenny, Eimear Lapalainien, Tuuli Levy, Daniel Liu, Chunyu Liu, Yongmei Loos, Ruth J.F. Lu, Ake Matise, Tara North, Kari E. Park, Sungshim L. Ratliff, Scott M. Reiner, Alex Rich, Stephen S. Rotter, Jerome I. Smith, Jennifer A. Sotoodehnia, Nona Tracy, Russell Van den Berg, David Xu, Huichun Ye, Ting Zhao, Wei Raffield, Laura M. Kooperberg, Charles |
| description | 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 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 |
| doi_str_mv | 10.1080/15592294.2024.2333668 |
| format | Article |
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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.</description><identifier>ISSN: 1559-2294</identifier><identifier>ISSN: 1559-2308</identifier><identifier>EISSN: 1559-2308</identifier><identifier>DOI: 10.1080/15592294.2024.2333668</identifier><identifier>PMID: 38571307</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>C-reactive protein ; C-Reactive Protein - genetics ; causal pathway ; CpG Islands ; DNA ; DNA Methylation ; Epigenesis, Genetic ; epigenetics ; EWAS ; Genome-Wide Association Study ; Humans ; Inflammation ; Inflammation - genetics ; Intracellular Signaling Peptides and Proteins - genetics ; Mendelian randomization ; methylation ; racial and ethnic diversity</subject><ispartof>Epigenetics, 2024-12, Vol.19 (1), p.2333668</ispartof><rights>2024 The Author(s). 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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.</description><subject>C-reactive protein</subject><subject>C-Reactive Protein - genetics</subject><subject>causal pathway</subject><subject>CpG Islands</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>epigenetics</subject><subject>EWAS</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Mendelian randomization</subject><subject>methylation</subject><subject>racial and ethnic diversity</subject><issn>1559-2294</issn><issn>1559-2308</issn><issn>1559-2308</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNp9kUtv1DAUha0KRNuBnwDKkk2Knev4sQON6EMqYgNr6ya2W1eZeLA9VPPv8TQzXSJZflx99xzbh5CPjF4xqugX1ve66zS_6mhXJwAQQp2Ri0O97YCqN6d9hc7JZc5PlHIQWr8j56B6yYDKC-J_uPK4n7CEODdbLMWlOTeYcxwDFmeb51Aem3WbHI4l_HXNNsXiwtzUkbAy07RvcLZNlZnD-HK0lUu5onG7W5Tze_LW45Tdh-O6Ir-vv_9a37b3P2_u1t_u25F3srRMKaa9cD3l3IFzUlgLUjMQ44C9F54q1IPstVVSeYuK284OXIDSFDsNsCJ3i66N-GS2KWww7U3EYF4KMT0YTCWMkzNeaN4xDZZLx1FS3Q96YNKCoPVzHK1anxet-uQ_O5eL2YQ8umnC2cVdNkABKFVQfVekX9AxxZyT86_WjJpDXOYUlznEZY5x1b5PR4vdsHH2teuUTwW-LkCYfUwbfI5psqbgforJJ5zHUO_xf49_zWqklQ</recordid><startdate>20241231</startdate><enddate>20241231</enddate><creator>Lundin, Jessica I.</creator><creator>Peters, Ulrike</creator><creator>Hu, Yao</creator><creator>Ammous, Farah</creator><creator>Avery, Christy L.</creator><creator>Benjamin, Emelia J.</creator><creator>Bis, Joshua C.</creator><creator>Brody, Jennifer A.</creator><creator>Carlson, Chris</creator><creator>Cushman, Mary</creator><creator>Gignoux, Chris</creator><creator>Guo, Xiuqing</creator><creator>Haessler, Jeff</creator><creator>Haiman, Chris</creator><creator>Joehanes, Roby</creator><creator>Kasela, Silva</creator><creator>Kenny, Eimear</creator><creator>Lapalainien, Tuuli</creator><creator>Levy, Daniel</creator><creator>Liu, Chunyu</creator><creator>Liu, Yongmei</creator><creator>Loos, Ruth J.F.</creator><creator>Lu, Ake</creator><creator>Matise, Tara</creator><creator>North, Kari E.</creator><creator>Park, Sungshim L.</creator><creator>Ratliff, Scott M.</creator><creator>Reiner, Alex</creator><creator>Rich, Stephen S.</creator><creator>Rotter, Jerome I.</creator><creator>Smith, Jennifer A.</creator><creator>Sotoodehnia, Nona</creator><creator>Tracy, Russell</creator><creator>Van den Berg, David</creator><creator>Xu, Huichun</creator><creator>Ye, Ting</creator><creator>Zhao, Wei</creator><creator>Raffield, Laura M.</creator><creator>Kooperberg, Charles</creator><general>Taylor & Francis</general><general>Taylor & Francis Group</general><scope>0YH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-4362-0034</orcidid><orcidid>https://orcid.org/0000-0003-3872-7793</orcidid><orcidid>https://orcid.org/0000-0003-4892-6235</orcidid><orcidid>https://orcid.org/0000-0002-7746-8109</orcidid><orcidid>https://orcid.org/0000-0003-4076-2336</orcidid></search><sort><creationdate>20241231</creationdate><title>Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations</title><author>Lundin, Jessica I. ; Peters, Ulrike ; Hu, Yao ; Ammous, Farah ; Avery, Christy L. ; Benjamin, Emelia J. ; Bis, Joshua C. ; Brody, Jennifer A. ; Carlson, Chris ; Cushman, Mary ; Gignoux, Chris ; Guo, Xiuqing ; Haessler, Jeff ; Haiman, Chris ; Joehanes, Roby ; Kasela, Silva ; Kenny, Eimear ; Lapalainien, Tuuli ; Levy, Daniel ; Liu, Chunyu ; Liu, Yongmei ; Loos, Ruth J.F. ; Lu, Ake ; Matise, Tara ; North, Kari E. ; Park, Sungshim L. ; Ratliff, Scott M. ; Reiner, Alex ; Rich, Stephen S. ; Rotter, Jerome I. ; Smith, Jennifer A. ; Sotoodehnia, Nona ; Tracy, Russell ; Van den Berg, David ; Xu, Huichun ; Ye, Ting ; Zhao, Wei ; Raffield, Laura M. ; Kooperberg, Charles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-18819f6e5044e3ee76dd379136cba5f6f08a9b759d878fda84d2db463890a2933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>C-reactive protein</topic><topic>C-Reactive Protein - 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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. 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| identifier | ISSN: 1559-2294 |
| ispartof | Epigenetics, 2024-12, Vol.19 (1), p.2333668 |
| issn | 1559-2294 1559-2308 1559-2308 |
| language | eng |
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| source | Taylor & Francis Open Access; MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central |
| subjects | C-reactive protein C-Reactive Protein - genetics causal pathway CpG Islands DNA DNA Methylation Epigenesis, Genetic epigenetics EWAS Genome-Wide Association Study Humans Inflammation Inflammation - genetics Intracellular Signaling Peptides and Proteins - genetics Mendelian randomization methylation racial and ethnic diversity |
| title | Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations |
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