DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases

  1. Ligthart, Symen
  2. Marzi, Carola
  3. Aslibekyan, Stella
  4. Mendelson, Michael M.
  5. Conneely, Karen N.
  6. Tanaka, Toshiko
  7. Colicino, Elena
  8. Waite, Lindsay L.
  9. Joehanes, Roby
  10. Guan, Weihua
  11. Brody, Jennifer A.
  12. Elks, Cathy
  13. Marioni, Riccardo
  14. Jhun, Min A.
  15. Agha, Golareh
  16. Bressler, Jan
  17. Ward-Caviness, Cavin K.
  18. Chen, Brian H.
  19. Huan, Tianxiao
  20. Bakulski, Kelly
  21. Salfati, Elias L.
  22. Fiorito, Giovanni
  23. Wahl, Simone
  24. Schramm, Katharina
  25. Sha, Jin
  26. Hernandez, Dena G.
  27. Just, Allan C.
  28. Smith, Jennifer A.
  29. Sotoodehnia, Nona
  30. Pilling, Luke C.
  31. Pankow, James S.
  32. Tsao, Phil S.
  33. Liu, Chunyu
  34. Zhao, Wei
  35. Guarrera, Simonetta
  36. Michopoulos, Vasiliki J.
  37. Smith, Alicia K.
  38. Peters, Marjolein J.
  39. Melzer, David
  40. Vokonas, Pantel
  41. Fornage, Myriam
  42. Prokisch, Holger
  43. Bis, Joshua C.
  44. Chu, Audrey Y.
  45. Herder, Christian
  46. Grallert, Harald
  47. Yao, Chen
  48. Shah, Sonia
  49. McRae, Allan F.
  50. Lin, Honghuang
  51. Horvath, Steve
  52. Fallin, Daniele
  53. Hofman, Albert
  54. Wareham, Nicholas J.
  55. Wiggins, Kerri L.
  56. Feinberg, Andrew P.
  57. Starr, John M.
  58. Visscher, Peter M.
  59. Murabito, Joanne M.
  60. Kardia, Sharon L. R.
  61. Absher, Devin M.
  62. Binder, Elisabeth B.
  63. Singleton, Andrew B.
  64. Bandinelli, Stefania
  65. Peters, Annette
  66. Waldenberger, Melanie
  67. Matullo, Giuseppe
  68. Schwartz, Joel D.
  69. Demerath, Ellen W.
  70. Uitterlinden, André G.
  71. van Meurs, Joyce B. J.
  72. Franco, Oscar H.
  73. Chen, Yii-Der Ida
  74. Levy, Daniel
  75. Turner, Stephen T.
  76. Deary, Ian J.
  77. Ressler, Kerry J.
  78. Dupuis, Josée
  79. Ferrucci, Luigi
  80. Ong, Ken K.
  81. Assimes, Themistocles L.
  82. Boerwinkle, Eric
  83. Koenig, Wolfgang
  84. Arnett, Donna K.
  85. Baccarelli, Andrea A.
  86. Benjamin, Emilia J.
  87. Dehghan, Abbas

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1000 Titel
  • DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases
1000 Autor/in
  1. Ligthart, Symen |
  2. Marzi, Carola |
  3. Aslibekyan, Stella |
  4. Mendelson, Michael M. |
  5. Conneely, Karen N. |
  6. Tanaka, Toshiko |
  7. Colicino, Elena |
  8. Waite, Lindsay L. |
  9. Joehanes, Roby |
  10. Guan, Weihua |
  11. Brody, Jennifer A. |
  12. Elks, Cathy |
  13. Marioni, Riccardo |
  14. Jhun, Min A. |
  15. Agha, Golareh |
  16. Bressler, Jan |
  17. Ward-Caviness, Cavin K. |
  18. Chen, Brian H. |
  19. Huan, Tianxiao |
  20. Bakulski, Kelly |
  21. Salfati, Elias L. |
  22. Fiorito, Giovanni |
  23. Wahl, Simone |
  24. Schramm, Katharina |
  25. Sha, Jin |
  26. Hernandez, Dena G. |
  27. Just, Allan C. |
  28. Smith, Jennifer A. |
  29. Sotoodehnia, Nona |
  30. Pilling, Luke C. |
  31. Pankow, James S. |
  32. Tsao, Phil S. |
  33. Liu, Chunyu |
  34. Zhao, Wei |
  35. Guarrera, Simonetta |
  36. Michopoulos, Vasiliki J. |
  37. Smith, Alicia K. |
  38. Peters, Marjolein J. |
  39. Melzer, David |
  40. Vokonas, Pantel |
  41. Fornage, Myriam |
  42. Prokisch, Holger |
  43. Bis, Joshua C. |
  44. Chu, Audrey Y. |
  45. Herder, Christian |
  46. Grallert, Harald |
  47. Yao, Chen |
  48. Shah, Sonia |
  49. McRae, Allan F. |
  50. Lin, Honghuang |
  51. Horvath, Steve |
  52. Fallin, Daniele |
  53. Hofman, Albert |
  54. Wareham, Nicholas J. |
  55. Wiggins, Kerri L. |
  56. Feinberg, Andrew P. |
  57. Starr, John M. |
  58. Visscher, Peter M. |
  59. Murabito, Joanne M. |
  60. Kardia, Sharon L. R. |
  61. Absher, Devin M. |
  62. Binder, Elisabeth B. |
  63. Singleton, Andrew B. |
  64. Bandinelli, Stefania |
  65. Peters, Annette |
  66. Waldenberger, Melanie |
  67. Matullo, Giuseppe |
  68. Schwartz, Joel D. |
  69. Demerath, Ellen W. |
  70. Uitterlinden, André G. |
  71. van Meurs, Joyce B. J. |
  72. Franco, Oscar H. |
  73. Chen, Yii-Der Ida |
  74. Levy, Daniel |
  75. Turner, Stephen T. |
  76. Deary, Ian J. |
  77. Ressler, Kerry J. |
  78. Dupuis, Josée |
  79. Ferrucci, Luigi |
  80. Ong, Ken K. |
  81. Assimes, Themistocles L. |
  82. Boerwinkle, Eric |
  83. Koenig, Wolfgang |
  84. Arnett, Donna K. |
  85. Baccarelli, Andrea A. |
  86. Benjamin, Emilia J. |
  87. Dehghan, Abbas |
1000 Erscheinungsjahr 2016
1000 LeibnizOpen
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2016-12-12
1000 Erschienen in
1000 Quellenangabe
  • 17:255
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2016
1000 Lizenz
1000 Verlagsversion
  • https://dx.doi.org/10.1186%2Fs13059-016-1119-5 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5151130/ |
1000 Ergänzendes Material
  • https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1119-5#Declarations |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • BACKGROUND: 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. RESULTS: 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 × 10–7) in the discovery panel of European ancestry and replicated (P < 2.29 × 10–4) 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 × 10–5), ten (17%) CpG sites were associated with a nearby genetic variant (P < 2.50 × 10–3), and 51 (88%) were also associated with at least one related cardiometabolic entity (P < 9.58 × 10–5). 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. CONCLUSION: 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.
1000 Sacherschließung
lokal Body mass index
lokal C-reactive protein
lokal DNA methylation
lokal Epigenome-wide association study
lokal Inflammation
lokal Diabetes
lokal Coronary heart disease
1000 Fachgruppe
  1. Medizin |
  2. Biologie |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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1000 Förderer
  1. National Heart, Lung, and Blood Institute (NHLBI) |
  2. National Institutes of Health (NIH) |
  3. National Institute on Aging (NIA) |
  4. Laughlin Family |
  5. Alpha Phi Foundation |
  6. Locke Charitable Foundation |
  7. National Center for Advancing Translational Sciences (CTSI) |
  8. National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) |
  9. Medical Research Council (MRC) |
  10. Cancer Research UK |
  11. MRC Cambridge initiative in metabolomic science |
  12. Division of Intramural Research |
  13. Center for Information Technology |
  14. Bethesda |
  15. MD |
  16. Tommy Kaplan Fund |
  17. Boston Children’s Hospital |
  18. Helmholtz Zentrum München – German Research Center for Environmental Health |
  19. Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität |
  20. European Union’s Seventh Framework Programme |
  21. SysVasc |
  22. PAIN-OMICS |
  23. German Federal Ministry of Education and Research (BMBF) |
  24. German National Genome Research Network (NGFNplus) |
  25. University of Ulm |
  26. Genetic Laboratory of the Department of Internal Medicine |
  27. Erasmus Medical Center (Erasmus MC) |
  28. Netherlands Organization for Scientific Research (NWO) |
  29. Erasmus University, Rotterdam |
  30. Netherlands Organization for the Health Research and Development |
  31. Research Institute for Diseases in the Elderly (RIDE) |
  32. Ministry of Education, Culture and Science |
  33. Ministry for Health, Welfare and Sports |
  34. European Commission |
  35. Municipality of Rotterdam |
1000 Fördernummer
  1. HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL105756, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652, R01HL092111, R01HL105756, R01HL103612, R01HL111089, R01HL116747, R01HL120393, 1RO1 HL64753, R01 HL076784, 1R01 AG028321, 1P50HL120163, HL054457, HL100185, HL119443
  2. 5RC2HL102419
  3. R01AG023629, N01-HC-25195, HHSN268201500001I, R01HL104135
  4. -
  5. -
  6. -
  7. UL1TR000124
  8. DK063491
  9. G9502233, G0401527, MC_UU_12015/1, MC_UU_12015/2
  10. C864/A8257
  11. MR/L00002/1
  12. -
  13. -
  14. -
  15. -
  16. -
  17. -
  18. -
  19. -
  20. FP7/2007-2013
  21. 603288
  22. HEALTH-F2-2013-602736
  23. -
  24. 01GS0834
  25. -
  26. -
  27. -
  28. 184021007
  29. -
  30. -
  31. -
  32. -
  33. -
  34. DG XII
  35. -
1000 Förderprogramm
  1. -
  2. Director’s Challenge Award
  3. -
  4. -
  5. -
  6. -
  7. -
  8. -
  9. -
  10. -
  11. -
  12. -
  13. -
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  19. LMUinnovativ
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  21. -
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  23. e:AtheroSysMed
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  28. -
  29. -
  30. ZonMw
  31. -
  32. -
  33. -
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1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer National Heart, Lung, and Blood Institute (NHLBI) |
    1000 Förderprogramm -
    1000 Fördernummer HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL105756, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652, R01HL092111, R01HL105756, R01HL103612, R01HL111089, R01HL116747, R01HL120393, 1RO1 HL64753, R01 HL076784, 1R01 AG028321, 1P50HL120163, HL054457, HL100185, HL119443
  2. 1000 joinedFunding-child
    1000 Förderer National Institutes of Health (NIH) |
    1000 Förderprogramm Director’s Challenge Award
    1000 Fördernummer 5RC2HL102419
  3. 1000 joinedFunding-child
    1000 Förderer National Institute on Aging (NIA) |
    1000 Förderprogramm -
    1000 Fördernummer R01AG023629, N01-HC-25195, HHSN268201500001I, R01HL104135
  4. 1000 joinedFunding-child
    1000 Förderer Laughlin Family |
    1000 Förderprogramm -
    1000 Fördernummer -
  5. 1000 joinedFunding-child
    1000 Förderer Alpha Phi Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  6. 1000 joinedFunding-child
    1000 Förderer Locke Charitable Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  7. 1000 joinedFunding-child
    1000 Förderer National Center for Advancing Translational Sciences (CTSI) |
    1000 Förderprogramm -
    1000 Fördernummer UL1TR000124
  8. 1000 joinedFunding-child
    1000 Förderer National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) |
    1000 Förderprogramm -
    1000 Fördernummer DK063491
  9. 1000 joinedFunding-child
    1000 Förderer Medical Research Council (MRC) |
    1000 Förderprogramm -
    1000 Fördernummer G9502233, G0401527, MC_UU_12015/1, MC_UU_12015/2
  10. 1000 joinedFunding-child
    1000 Förderer Cancer Research UK |
    1000 Förderprogramm -
    1000 Fördernummer C864/A8257
  11. 1000 joinedFunding-child
    1000 Förderer MRC Cambridge initiative in metabolomic science |
    1000 Förderprogramm -
    1000 Fördernummer MR/L00002/1
  12. 1000 joinedFunding-child
    1000 Förderer Division of Intramural Research |
    1000 Förderprogramm -
    1000 Fördernummer -
  13. 1000 joinedFunding-child
    1000 Förderer Center for Information Technology |
    1000 Förderprogramm -
    1000 Fördernummer -
  14. 1000 joinedFunding-child
    1000 Förderer Bethesda |
    1000 Förderprogramm -
    1000 Fördernummer -
  15. 1000 joinedFunding-child
    1000 Förderer MD |
    1000 Förderprogramm -
    1000 Fördernummer -
  16. 1000 joinedFunding-child
    1000 Förderer Tommy Kaplan Fund |
    1000 Förderprogramm -
    1000 Fördernummer -
  17. 1000 joinedFunding-child
    1000 Förderer Boston Children’s Hospital |
    1000 Förderprogramm -
    1000 Fördernummer -
  18. 1000 joinedFunding-child
    1000 Förderer Helmholtz Zentrum München – German Research Center for Environmental Health |
    1000 Förderprogramm -
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1000 @id frl:6408134.rdf
1000 Erstellt am 2018-05-28T13:31:31.134+0200
1000 Erstellt von 218
1000 beschreibt frl:6408134
1000 Bearbeitet von 122
1000 Zuletzt bearbeitet Fri Jun 29 11:28:47 CEST 2018
1000 Objekt bearb. Fri Jun 29 11:28:12 CEST 2018
1000 Vgl. frl:6408134
1000 Oai Id
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1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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