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

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. and Dehghan, Abbas (2016) DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases. Genome Biology, 17 1: 255-255. doi:10.1186/s13059-016-1119-5


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
Title DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases
Journal name Genome Biology   Check publisher's open access policy
ISSN 1474-760X
1474-7596
Publication date 2016-12-12
Sub-type Article (original research)
DOI 10.1186/s13059-016-1119-5
Open Access Status DOI
Volume 17
Issue 1
Start page 255
End page 255
Total pages 15
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
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.
Formatted abstract
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.
Keyword Body mass index
C-reactive protein
Coronary heart disease
Diabetes
DNA methylation
Epigenome-wide association study
Inflammation
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID HHSN268201100012C
P50 HL120163
RC2 HL102419
R01 HL103612
HHSN268201100009I
R56 MH071537
R01 ES015172
R01 HL104135
R01 HL120393
R01 MH071537
HHSN268201100010C
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HHSN268200800007C
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M01 RR000039
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UL1 TR000124
N01HC55222
N01HC85086
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R01 AG042187
U10 HL054457
T32 HL098049
P30 DK063491
RC1 HL100185
HHSN268201100006C
HHSN268201200036C
P30 ES023515
HHSN268201100005I
U01 HL054457
HHSN268201500001I
UL1 TR000454
N01HC85082
HHSN268201100009C
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N01HC25195
HHSN268201100007I
N01HC85079
R01 AG028321
R01 AG023629
N01HC85080
R01 HL111089
R01 HL116747
R01 HL092111
N01HC85081
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
UQ Diamantina Institute Publications
 
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