DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases
Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation. We performed a...
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| Veröffentlicht in: | Genome Biology 2016-12, Vol.17 (1), p.255-255, Article 255 |
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| creator | Ligthart, Symen Marzi, Carola Aslibekyan, Stella Mendelson, Michael M Conneely, Karen N Tanaka, Toshiko Colicino, Elena Waite, Lindsay L Joehanes, Roby Guan, Weihua Brody, Jennifer A Elks, Cathy Marioni, Riccardo Jhun, Min A Agha, Golareh Bressler, Jan Ward-Caviness, Cavin K Chen, Brian H Huan, Tianxiao Bakulski, Kelly Salfati, Elias L Fiorito, Giovanni Wahl, Simone Schramm, Katharina Sha, Jin Hernandez, Dena G Just, Allan C Smith, Jennifer A Sotoodehnia, Nona Pilling, Luke C Pankow, James S Tsao, Phil S Liu, Chunyu Zhao, Wei Guarrera, Simonetta Michopoulos, Vasiliki J Smith, Alicia K Peters, Marjolein J Melzer, David Vokonas, Pantel Fornage, Myriam Prokisch, Holger Bis, Joshua C Chu, Audrey Y Herder, Christian Grallert, Harald Yao, Chen Shah, Sonia McRae, Allan F Lin, Honghuang Horvath, Steve Fallin, Daniele Hofman, Albert Wareham, Nicholas J Wiggins, Kerri L Feinberg, Andrew P Starr, John M Visscher, Peter M Murabito, Joanne M Kardia, Sharon L R Absher, Devin M Binder, Elisabeth B Singleton, Andrew B Bandinelli, Stefania Peters, Annette Waldenberger, Melanie Matullo, Giuseppe Schwartz, Joel D Demerath, Ellen W Uitterlinden, André G van Meurs, Joyce B J Franco, Oscar H Chen, Yii-Der Ida Levy, Daniel Turner, Stephen T Deary, Ian J Ressler, Kerry J Dupuis, Josée Ferrucci, Luigi Ong, Ken K Assimes, Themistocles L Boerwinkle, Eric Koenig, Wolfgang Arnett, Donna K Baccarelli, Andrea A Benjamin, Emelia J Dehghan, Abbas |
| description | Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.
We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P |
| doi_str_mv | 10.1186/s13059-016-1119-5 |
| format | Article |
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Marzi, Carola ; Aslibekyan, Stella ; Mendelson, Michael M ; Conneely, Karen N ; Tanaka, Toshiko ; Colicino, Elena ; Waite, Lindsay L ; Joehanes, Roby ; Guan, Weihua ; Brody, Jennifer A ; Elks, Cathy ; Marioni, Riccardo ; Jhun, Min A ; Agha, Golareh ; Bressler, Jan ; Ward-Caviness, Cavin K ; Chen, Brian H ; Huan, Tianxiao ; Bakulski, Kelly ; Salfati, Elias L ; Fiorito, Giovanni ; Wahl, Simone ; Schramm, Katharina ; Sha, Jin ; Hernandez, Dena G ; Just, Allan C ; Smith, Jennifer A ; Sotoodehnia, Nona ; Pilling, Luke C ; Pankow, James S ; Tsao, Phil S ; Liu, Chunyu ; Zhao, Wei ; Guarrera, Simonetta ; Michopoulos, Vasiliki J ; Smith, Alicia K ; Peters, Marjolein J ; Melzer, David ; Vokonas, Pantel ; Fornage, Myriam ; Prokisch, Holger ; Bis, Joshua C ; Chu, Audrey Y ; Herder, Christian ; Grallert, Harald ; Yao, Chen ; Shah, Sonia ; McRae, Allan F ; Lin, Honghuang ; Horvath, Steve ; Fallin, Daniele ; Hofman, Albert ; Wareham, Nicholas J ; Wiggins, Kerri L ; Feinberg, Andrew P ; Starr, John M ; Visscher, Peter M ; Murabito, Joanne M ; Kardia, Sharon L R ; Absher, Devin M ; Binder, Elisabeth B ; Singleton, Andrew B ; Bandinelli, Stefania ; Peters, Annette ; Waldenberger, Melanie ; Matullo, Giuseppe ; Schwartz, Joel D ; Demerath, Ellen W ; Uitterlinden, André G ; van Meurs, Joyce B J ; Franco, Oscar H ; Chen, Yii-Der Ida ; Levy, Daniel ; Turner, Stephen T ; Deary, Ian J ; Ressler, Kerry J ; Dupuis, Josée ; Ferrucci, Luigi ; Ong, Ken K ; Assimes, Themistocles L ; Boerwinkle, Eric ; Koenig, Wolfgang ; Arnett, Donna K ; Baccarelli, Andrea A ; Benjamin, Emelia J ; Dehghan, Abbas</creator><creatorcontrib>Ligthart, Symen ; Marzi, Carola ; Aslibekyan, Stella ; Mendelson, Michael M ; Conneely, Karen N ; Tanaka, Toshiko ; Colicino, Elena ; Waite, Lindsay L ; Joehanes, Roby ; Guan, Weihua ; Brody, Jennifer A ; Elks, Cathy ; Marioni, Riccardo ; Jhun, Min A ; Agha, Golareh ; Bressler, Jan ; Ward-Caviness, Cavin K ; Chen, Brian H ; Huan, Tianxiao ; Bakulski, Kelly ; Salfati, Elias L ; Fiorito, Giovanni ; Wahl, Simone ; Schramm, Katharina ; Sha, Jin ; Hernandez, Dena G ; Just, Allan C ; Smith, Jennifer A ; Sotoodehnia, Nona ; Pilling, Luke C ; Pankow, James S ; Tsao, Phil S ; Liu, Chunyu ; Zhao, Wei ; Guarrera, Simonetta ; Michopoulos, Vasiliki J ; Smith, Alicia K ; Peters, Marjolein J ; Melzer, David ; Vokonas, Pantel ; Fornage, Myriam ; Prokisch, Holger ; Bis, Joshua C ; Chu, Audrey Y ; Herder, Christian ; Grallert, Harald ; Yao, Chen ; Shah, Sonia ; McRae, Allan F ; Lin, Honghuang ; Horvath, Steve ; Fallin, Daniele ; Hofman, Albert ; Wareham, Nicholas J ; Wiggins, Kerri L ; Feinberg, Andrew P ; Starr, John M ; Visscher, Peter M ; Murabito, Joanne M ; Kardia, Sharon L R ; Absher, Devin M ; Binder, Elisabeth B ; Singleton, Andrew B ; Bandinelli, Stefania ; Peters, Annette ; Waldenberger, Melanie ; Matullo, Giuseppe ; Schwartz, Joel D ; Demerath, Ellen W ; Uitterlinden, André G ; van Meurs, Joyce B J ; Franco, Oscar H ; Chen, Yii-Der Ida ; Levy, Daniel ; Turner, Stephen T ; Deary, Ian J ; Ressler, Kerry J ; Dupuis, Josée ; Ferrucci, Luigi ; Ong, Ken K ; Assimes, Themistocles L ; Boerwinkle, Eric ; Koenig, Wolfgang ; Arnett, Donna K ; Baccarelli, Andrea A ; Benjamin, Emelia J ; Dehghan, Abbas ; CHARGE epigenetics of Coronary Heart Disease ; WHI-EMPC Investigators</creatorcontrib><description>Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.
We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10
) in the discovery panel of European ancestry and replicated (P < 2.29 × 10
) 58 CpG sites (45 unique loci) among African Americans. To further characterize the molecular and clinical relevance of the findings, we examined the association with gene expression, genetic sequence variants, and clinical outcomes. DNA methylation at nine (16%) CpG sites was associated with whole blood gene expression in cis (P < 8.47 × 10
), ten (17%) CpG sites were associated with a nearby genetic variant (P < 2.50 × 10
), and 51 (88%) were also associated with at least one related cardiometabolic entity (P < 9.58 × 10
). An additive weighted score of replicated CpG sites accounted for up to 6% inter-individual variation (R2) of age-adjusted and sex-adjusted CRP, independent of known CRP-related genetic variants.
We have completed an EWAS of chronic low-grade inflammation and identified many novel genetic loci underlying inflammation that may serve as targets for the development of novel therapeutic interventions for inflammation.</description><identifier>ISSN: 1474-760X</identifier><identifier>ISSN: 1474-7596</identifier><identifier>EISSN: 1474-760X</identifier><identifier>DOI: 10.1186/s13059-016-1119-5</identifier><identifier>PMID: 27955697</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>African Americans ; Analysis ; ancestry ; blood serum ; Body mass index ; C-reactive protein ; C-Reactive Protein - genetics ; Coronary heart disease ; CpG islands ; CpG Islands - genetics ; Diabetes ; DNA methylation ; DNA Methylation - genetics ; Epigenesis, Genetic ; Epigenetics ; European Continental Ancestry Group ; Female ; Gene Expression ; Genetic aspects ; Genetic diversity ; Genetic Variation ; Genome-Wide Association Study ; Health aspects ; Humans ; Immune response ; Inflammation ; Inflammation - blood ; Inflammation - genetics ; loci ; Male ; meta-analysis ; Method ; Nucleotide Motifs - genetics ; Nucleotide sequence ; pathogenesis ; Quantitative Trait Loci - genetics ; Risk factors ; Studies ; Therapeutic applications</subject><ispartof>Genome Biology, 2016-12, Vol.17 (1), p.255-255, Article 255</ispartof><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>2016. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s). 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c595t-7fc0ea959bff4c89a58a5aa0ae01e63a63082960ad4c88657753714842af41b3</citedby><cites>FETCH-LOGICAL-c595t-7fc0ea959bff4c89a58a5aa0ae01e63a63082960ad4c88657753714842af41b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5151130/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5151130/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27955697$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ligthart, Symen</creatorcontrib><creatorcontrib>Marzi, Carola</creatorcontrib><creatorcontrib>Aslibekyan, Stella</creatorcontrib><creatorcontrib>Mendelson, Michael M</creatorcontrib><creatorcontrib>Conneely, Karen N</creatorcontrib><creatorcontrib>Tanaka, Toshiko</creatorcontrib><creatorcontrib>Colicino, Elena</creatorcontrib><creatorcontrib>Waite, Lindsay L</creatorcontrib><creatorcontrib>Joehanes, Roby</creatorcontrib><creatorcontrib>Guan, Weihua</creatorcontrib><creatorcontrib>Brody, Jennifer A</creatorcontrib><creatorcontrib>Elks, Cathy</creatorcontrib><creatorcontrib>Marioni, Riccardo</creatorcontrib><creatorcontrib>Jhun, Min A</creatorcontrib><creatorcontrib>Agha, Golareh</creatorcontrib><creatorcontrib>Bressler, Jan</creatorcontrib><creatorcontrib>Ward-Caviness, Cavin K</creatorcontrib><creatorcontrib>Chen, Brian H</creatorcontrib><creatorcontrib>Huan, Tianxiao</creatorcontrib><creatorcontrib>Bakulski, Kelly</creatorcontrib><creatorcontrib>Salfati, Elias L</creatorcontrib><creatorcontrib>Fiorito, Giovanni</creatorcontrib><creatorcontrib>Wahl, Simone</creatorcontrib><creatorcontrib>Schramm, Katharina</creatorcontrib><creatorcontrib>Sha, Jin</creatorcontrib><creatorcontrib>Hernandez, Dena G</creatorcontrib><creatorcontrib>Just, Allan C</creatorcontrib><creatorcontrib>Smith, Jennifer A</creatorcontrib><creatorcontrib>Sotoodehnia, Nona</creatorcontrib><creatorcontrib>Pilling, Luke C</creatorcontrib><creatorcontrib>Pankow, James S</creatorcontrib><creatorcontrib>Tsao, Phil S</creatorcontrib><creatorcontrib>Liu, Chunyu</creatorcontrib><creatorcontrib>Zhao, Wei</creatorcontrib><creatorcontrib>Guarrera, Simonetta</creatorcontrib><creatorcontrib>Michopoulos, Vasiliki J</creatorcontrib><creatorcontrib>Smith, Alicia K</creatorcontrib><creatorcontrib>Peters, Marjolein J</creatorcontrib><creatorcontrib>Melzer, David</creatorcontrib><creatorcontrib>Vokonas, Pantel</creatorcontrib><creatorcontrib>Fornage, Myriam</creatorcontrib><creatorcontrib>Prokisch, Holger</creatorcontrib><creatorcontrib>Bis, Joshua C</creatorcontrib><creatorcontrib>Chu, Audrey Y</creatorcontrib><creatorcontrib>Herder, Christian</creatorcontrib><creatorcontrib>Grallert, Harald</creatorcontrib><creatorcontrib>Yao, Chen</creatorcontrib><creatorcontrib>Shah, Sonia</creatorcontrib><creatorcontrib>McRae, Allan F</creatorcontrib><creatorcontrib>Lin, Honghuang</creatorcontrib><creatorcontrib>Horvath, Steve</creatorcontrib><creatorcontrib>Fallin, Daniele</creatorcontrib><creatorcontrib>Hofman, Albert</creatorcontrib><creatorcontrib>Wareham, Nicholas J</creatorcontrib><creatorcontrib>Wiggins, Kerri L</creatorcontrib><creatorcontrib>Feinberg, Andrew P</creatorcontrib><creatorcontrib>Starr, John M</creatorcontrib><creatorcontrib>Visscher, Peter M</creatorcontrib><creatorcontrib>Murabito, Joanne M</creatorcontrib><creatorcontrib>Kardia, Sharon L R</creatorcontrib><creatorcontrib>Absher, Devin M</creatorcontrib><creatorcontrib>Binder, Elisabeth B</creatorcontrib><creatorcontrib>Singleton, Andrew B</creatorcontrib><creatorcontrib>Bandinelli, Stefania</creatorcontrib><creatorcontrib>Peters, Annette</creatorcontrib><creatorcontrib>Waldenberger, Melanie</creatorcontrib><creatorcontrib>Matullo, Giuseppe</creatorcontrib><creatorcontrib>Schwartz, Joel D</creatorcontrib><creatorcontrib>Demerath, Ellen W</creatorcontrib><creatorcontrib>Uitterlinden, André G</creatorcontrib><creatorcontrib>van Meurs, Joyce B J</creatorcontrib><creatorcontrib>Franco, Oscar H</creatorcontrib><creatorcontrib>Chen, Yii-Der Ida</creatorcontrib><creatorcontrib>Levy, Daniel</creatorcontrib><creatorcontrib>Turner, Stephen T</creatorcontrib><creatorcontrib>Deary, Ian J</creatorcontrib><creatorcontrib>Ressler, Kerry J</creatorcontrib><creatorcontrib>Dupuis, Josée</creatorcontrib><creatorcontrib>Ferrucci, Luigi</creatorcontrib><creatorcontrib>Ong, Ken K</creatorcontrib><creatorcontrib>Assimes, Themistocles L</creatorcontrib><creatorcontrib>Boerwinkle, Eric</creatorcontrib><creatorcontrib>Koenig, Wolfgang</creatorcontrib><creatorcontrib>Arnett, Donna K</creatorcontrib><creatorcontrib>Baccarelli, Andrea A</creatorcontrib><creatorcontrib>Benjamin, Emelia J</creatorcontrib><creatorcontrib>Dehghan, Abbas</creatorcontrib><creatorcontrib>CHARGE epigenetics of Coronary Heart Disease</creatorcontrib><creatorcontrib>WHI-EMPC Investigators</creatorcontrib><title>DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases</title><title>Genome Biology</title><addtitle>Genome Biol</addtitle><description>Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.
We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10
) in the discovery panel of European ancestry and replicated (P < 2.29 × 10
) 58 CpG sites (45 unique loci) among African Americans. To further characterize the molecular and clinical relevance of the findings, we examined the association with gene expression, genetic sequence variants, and clinical outcomes. DNA methylation at nine (16%) CpG sites was associated with whole blood gene expression in cis (P < 8.47 × 10
), ten (17%) CpG sites were associated with a nearby genetic variant (P < 2.50 × 10
), and 51 (88%) were also associated with at least one related cardiometabolic entity (P < 9.58 × 10
). An additive weighted score of replicated CpG sites accounted for up to 6% inter-individual variation (R2) of age-adjusted and sex-adjusted CRP, independent of known CRP-related genetic variants.
We have completed an EWAS of chronic low-grade inflammation and identified many novel genetic loci underlying inflammation that may serve as targets for the development of novel therapeutic interventions for inflammation.</description><subject>African Americans</subject><subject>Analysis</subject><subject>ancestry</subject><subject>blood serum</subject><subject>Body mass index</subject><subject>C-reactive protein</subject><subject>C-Reactive Protein - genetics</subject><subject>Coronary heart disease</subject><subject>CpG islands</subject><subject>CpG Islands - genetics</subject><subject>Diabetes</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>European Continental Ancestry Group</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic Variation</subject><subject>Genome-Wide Association Study</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immune response</subject><subject>Inflammation</subject><subject>Inflammation - blood</subject><subject>Inflammation - genetics</subject><subject>loci</subject><subject>Male</subject><subject>meta-analysis</subject><subject>Method</subject><subject>Nucleotide Motifs - genetics</subject><subject>Nucleotide sequence</subject><subject>pathogenesis</subject><subject>Quantitative Trait Loci - genetics</subject><subject>Risk factors</subject><subject>Studies</subject><subject>Therapeutic 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diseases</title><author>Ligthart, Symen ; Marzi, Carola ; Aslibekyan, Stella ; Mendelson, Michael M ; Conneely, Karen N ; Tanaka, Toshiko ; Colicino, Elena ; Waite, Lindsay L ; Joehanes, Roby ; Guan, Weihua ; Brody, Jennifer A ; Elks, Cathy ; Marioni, Riccardo ; Jhun, Min A ; Agha, Golareh ; Bressler, Jan ; Ward-Caviness, Cavin K ; Chen, Brian H ; Huan, Tianxiao ; Bakulski, Kelly ; Salfati, Elias L ; Fiorito, Giovanni ; Wahl, Simone ; Schramm, Katharina ; Sha, Jin ; Hernandez, Dena G ; Just, Allan C ; Smith, Jennifer A ; Sotoodehnia, Nona ; Pilling, Luke C ; Pankow, James S ; Tsao, Phil S ; Liu, Chunyu ; Zhao, Wei ; Guarrera, Simonetta ; Michopoulos, Vasiliki J ; Smith, Alicia K ; Peters, Marjolein J ; Melzer, David ; Vokonas, Pantel ; Fornage, Myriam ; Prokisch, Holger ; Bis, Joshua C ; Chu, Audrey Y ; Herder, Christian ; Grallert, Harald ; Yao, Chen ; Shah, Sonia ; McRae, Allan F ; Lin, Honghuang ; Horvath, Steve ; Fallin, Daniele ; Hofman, Albert ; Wareham, Nicholas J ; Wiggins, Kerri L ; Feinberg, Andrew P ; Starr, John M ; Visscher, Peter M ; Murabito, Joanne M ; Kardia, Sharon L R ; Absher, Devin M ; Binder, Elisabeth B ; Singleton, Andrew B ; Bandinelli, Stefania ; Peters, Annette ; Waldenberger, Melanie ; Matullo, Giuseppe ; Schwartz, Joel D ; Demerath, Ellen W ; Uitterlinden, André G ; van Meurs, Joyce B J ; Franco, Oscar H ; Chen, Yii-Der Ida ; Levy, Daniel ; Turner, Stephen T ; Deary, Ian J ; Ressler, Kerry J ; Dupuis, Josée ; Ferrucci, Luigi ; Ong, Ken K ; Assimes, Themistocles L ; Boerwinkle, Eric ; Koenig, Wolfgang ; Arnett, Donna K ; Baccarelli, Andrea A ; Benjamin, Emelia J ; Dehghan, Abbas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c595t-7fc0ea959bff4c89a58a5aa0ae01e63a63082960ad4c88657753714842af41b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>African Americans</topic><topic>Analysis</topic><topic>ancestry</topic><topic>blood serum</topic><topic>Body mass index</topic><topic>C-reactive protein</topic><topic>C-Reactive Protein - genetics</topic><topic>Coronary heart disease</topic><topic>CpG islands</topic><topic>CpG Islands - genetics</topic><topic>Diabetes</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>European Continental Ancestry Group</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic Variation</topic><topic>Genome-Wide Association Study</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Immune response</topic><topic>Inflammation</topic><topic>Inflammation - blood</topic><topic>Inflammation - genetics</topic><topic>loci</topic><topic>Male</topic><topic>meta-analysis</topic><topic>Method</topic><topic>Nucleotide Motifs - genetics</topic><topic>Nucleotide sequence</topic><topic>pathogenesis</topic><topic>Quantitative Trait Loci - genetics</topic><topic>Risk factors</topic><topic>Studies</topic><topic>Therapeutic applications</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ligthart, Symen</creatorcontrib><creatorcontrib>Marzi, Carola</creatorcontrib><creatorcontrib>Aslibekyan, Stella</creatorcontrib><creatorcontrib>Mendelson, Michael M</creatorcontrib><creatorcontrib>Conneely, Karen N</creatorcontrib><creatorcontrib>Tanaka, Toshiko</creatorcontrib><creatorcontrib>Colicino, Elena</creatorcontrib><creatorcontrib>Waite, Lindsay L</creatorcontrib><creatorcontrib>Joehanes, Roby</creatorcontrib><creatorcontrib>Guan, Weihua</creatorcontrib><creatorcontrib>Brody, Jennifer A</creatorcontrib><creatorcontrib>Elks, Cathy</creatorcontrib><creatorcontrib>Marioni, Riccardo</creatorcontrib><creatorcontrib>Jhun, Min A</creatorcontrib><creatorcontrib>Agha, Golareh</creatorcontrib><creatorcontrib>Bressler, Jan</creatorcontrib><creatorcontrib>Ward-Caviness, Cavin K</creatorcontrib><creatorcontrib>Chen, Brian H</creatorcontrib><creatorcontrib>Huan, Tianxiao</creatorcontrib><creatorcontrib>Bakulski, Kelly</creatorcontrib><creatorcontrib>Salfati, Elias L</creatorcontrib><creatorcontrib>Fiorito, Giovanni</creatorcontrib><creatorcontrib>Wahl, Simone</creatorcontrib><creatorcontrib>Schramm, Katharina</creatorcontrib><creatorcontrib>Sha, Jin</creatorcontrib><creatorcontrib>Hernandez, Dena G</creatorcontrib><creatorcontrib>Just, Allan C</creatorcontrib><creatorcontrib>Smith, Jennifer A</creatorcontrib><creatorcontrib>Sotoodehnia, Nona</creatorcontrib><creatorcontrib>Pilling, Luke C</creatorcontrib><creatorcontrib>Pankow, James S</creatorcontrib><creatorcontrib>Tsao, Phil S</creatorcontrib><creatorcontrib>Liu, Chunyu</creatorcontrib><creatorcontrib>Zhao, Wei</creatorcontrib><creatorcontrib>Guarrera, Simonetta</creatorcontrib><creatorcontrib>Michopoulos, Vasiliki J</creatorcontrib><creatorcontrib>Smith, Alicia K</creatorcontrib><creatorcontrib>Peters, Marjolein J</creatorcontrib><creatorcontrib>Melzer, David</creatorcontrib><creatorcontrib>Vokonas, Pantel</creatorcontrib><creatorcontrib>Fornage, Myriam</creatorcontrib><creatorcontrib>Prokisch, Holger</creatorcontrib><creatorcontrib>Bis, Joshua C</creatorcontrib><creatorcontrib>Chu, Audrey Y</creatorcontrib><creatorcontrib>Herder, Christian</creatorcontrib><creatorcontrib>Grallert, Harald</creatorcontrib><creatorcontrib>Yao, Chen</creatorcontrib><creatorcontrib>Shah, Sonia</creatorcontrib><creatorcontrib>McRae, Allan F</creatorcontrib><creatorcontrib>Lin, Honghuang</creatorcontrib><creatorcontrib>Horvath, Steve</creatorcontrib><creatorcontrib>Fallin, Daniele</creatorcontrib><creatorcontrib>Hofman, Albert</creatorcontrib><creatorcontrib>Wareham, Nicholas J</creatorcontrib><creatorcontrib>Wiggins, Kerri L</creatorcontrib><creatorcontrib>Feinberg, Andrew P</creatorcontrib><creatorcontrib>Starr, John M</creatorcontrib><creatorcontrib>Visscher, Peter M</creatorcontrib><creatorcontrib>Murabito, Joanne M</creatorcontrib><creatorcontrib>Kardia, Sharon L R</creatorcontrib><creatorcontrib>Absher, Devin M</creatorcontrib><creatorcontrib>Binder, Elisabeth B</creatorcontrib><creatorcontrib>Singleton, Andrew B</creatorcontrib><creatorcontrib>Bandinelli, Stefania</creatorcontrib><creatorcontrib>Peters, Annette</creatorcontrib><creatorcontrib>Waldenberger, Melanie</creatorcontrib><creatorcontrib>Matullo, Giuseppe</creatorcontrib><creatorcontrib>Schwartz, Joel D</creatorcontrib><creatorcontrib>Demerath, Ellen W</creatorcontrib><creatorcontrib>Uitterlinden, André G</creatorcontrib><creatorcontrib>van Meurs, Joyce B J</creatorcontrib><creatorcontrib>Franco, Oscar H</creatorcontrib><creatorcontrib>Chen, Yii-Der Ida</creatorcontrib><creatorcontrib>Levy, Daniel</creatorcontrib><creatorcontrib>Turner, 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College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genome Biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ligthart, Symen</au><au>Marzi, Carola</au><au>Aslibekyan, Stella</au><au>Mendelson, Michael M</au><au>Conneely, Karen N</au><au>Tanaka, Toshiko</au><au>Colicino, Elena</au><au>Waite, Lindsay L</au><au>Joehanes, Roby</au><au>Guan, Weihua</au><au>Brody, Jennifer A</au><au>Elks, Cathy</au><au>Marioni, Riccardo</au><au>Jhun, Min A</au><au>Agha, Golareh</au><au>Bressler, Jan</au><au>Ward-Caviness, Cavin K</au><au>Chen, Brian H</au><au>Huan, Tianxiao</au><au>Bakulski, Kelly</au><au>Salfati, Elias L</au><au>Fiorito, Giovanni</au><au>Wahl, Simone</au><au>Schramm, Katharina</au><au>Sha, Jin</au><au>Hernandez, Dena G</au><au>Just, Allan C</au><au>Smith, Jennifer A</au><au>Sotoodehnia, Nona</au><au>Pilling, Luke C</au><au>Pankow, James S</au><au>Tsao, Phil S</au><au>Liu, Chunyu</au><au>Zhao, Wei</au><au>Guarrera, Simonetta</au><au>Michopoulos, Vasiliki J</au><au>Smith, Alicia K</au><au>Peters, Marjolein J</au><au>Melzer, David</au><au>Vokonas, Pantel</au><au>Fornage, Myriam</au><au>Prokisch, Holger</au><au>Bis, Joshua C</au><au>Chu, Audrey Y</au><au>Herder, Christian</au><au>Grallert, Harald</au><au>Yao, Chen</au><au>Shah, Sonia</au><au>McRae, Allan F</au><au>Lin, Honghuang</au><au>Horvath, Steve</au><au>Fallin, Daniele</au><au>Hofman, Albert</au><au>Wareham, Nicholas J</au><au>Wiggins, Kerri L</au><au>Feinberg, Andrew P</au><au>Starr, John M</au><au>Visscher, Peter M</au><au>Murabito, Joanne M</au><au>Kardia, Sharon L R</au><au>Absher, Devin M</au><au>Binder, Elisabeth B</au><au>Singleton, Andrew B</au><au>Bandinelli, Stefania</au><au>Peters, Annette</au><au>Waldenberger, Melanie</au><au>Matullo, Giuseppe</au><au>Schwartz, Joel D</au><au>Demerath, Ellen W</au><au>Uitterlinden, André G</au><au>van Meurs, Joyce B J</au><au>Franco, Oscar H</au><au>Chen, Yii-Der Ida</au><au>Levy, Daniel</au><au>Turner, Stephen T</au><au>Deary, Ian J</au><au>Ressler, Kerry J</au><au>Dupuis, Josée</au><au>Ferrucci, Luigi</au><au>Ong, Ken K</au><au>Assimes, Themistocles L</au><au>Boerwinkle, Eric</au><au>Koenig, Wolfgang</au><au>Arnett, Donna K</au><au>Baccarelli, Andrea A</au><au>Benjamin, Emelia J</au><au>Dehghan, Abbas</au><aucorp>CHARGE epigenetics of Coronary Heart Disease</aucorp><aucorp>WHI-EMPC Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases</atitle><jtitle>Genome Biology</jtitle><addtitle>Genome Biol</addtitle><date>2016-12-12</date><risdate>2016</risdate><volume>17</volume><issue>1</issue><spage>255</spage><epage>255</epage><pages>255-255</pages><artnum>255</artnum><issn>1474-760X</issn><issn>1474-7596</issn><eissn>1474-760X</eissn><abstract>Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.
We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10
) in the discovery panel of European ancestry and replicated (P < 2.29 × 10
) 58 CpG sites (45 unique loci) among African Americans. To further characterize the molecular and clinical relevance of the findings, we examined the association with gene expression, genetic sequence variants, and clinical outcomes. DNA methylation at nine (16%) CpG sites was associated with whole blood gene expression in cis (P < 8.47 × 10
), ten (17%) CpG sites were associated with a nearby genetic variant (P < 2.50 × 10
), and 51 (88%) were also associated with at least one related cardiometabolic entity (P < 9.58 × 10
). An additive weighted score of replicated CpG sites accounted for up to 6% inter-individual variation (R2) of age-adjusted and sex-adjusted CRP, independent of known CRP-related genetic variants.
We have completed an EWAS of chronic low-grade inflammation and identified many novel genetic loci underlying inflammation that may serve as targets for the development of novel therapeutic interventions for inflammation.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>27955697</pmid><doi>10.1186/s13059-016-1119-5</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1474-760X |
| ispartof | Genome Biology, 2016-12, Vol.17 (1), p.255-255, Article 255 |
| issn | 1474-760X 1474-7596 1474-760X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5151130 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SpringerLink Journals - AutoHoldings; Springer Nature OA Free Journals |
| subjects | African Americans Analysis ancestry blood serum Body mass index C-reactive protein C-Reactive Protein - genetics Coronary heart disease CpG islands CpG Islands - genetics Diabetes DNA methylation DNA Methylation - genetics Epigenesis, Genetic Epigenetics European Continental Ancestry Group Female Gene Expression Genetic aspects Genetic diversity Genetic Variation Genome-Wide Association Study Health aspects Humans Immune response Inflammation Inflammation - blood Inflammation - genetics loci Male meta-analysis Method Nucleotide Motifs - genetics Nucleotide sequence pathogenesis Quantitative Trait Loci - genetics Risk factors Studies Therapeutic applications |
| title | DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases |
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