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

Genome Biol 2016 12 12;17(1):255. Epub 2016 Dec 12.

Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.

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) 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.

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.

Download full-text PDF

http://dx.doi.org/10.1186/s13059-016-1119-5DOI Listing
December 2016
142 Reads
24 Citations

Publication Analysis

Top Keywords

low-grade inflammation
chronic low-grade
complex diseases
dna methylation
therapeutic targets
targets inflammationresults
inflammationresults performed
meta-analysis epigenome-wide
performed meta-analysis
replication african
african americans
novel pathways
n = 4111 differential
associated chronic
loci dna
inflammation reveal
reveal novel
trans-ethnic replication
americans n = 4111
pathways therapeutic

Altmetric Statistics


(Supplied by CrossRef)
Article in Nat Immunol
GK Hansson et al.
Nat Immunol 2011
Article in Nat Rev Immunol
MY Donath et al.
Nat Rev Immunol 2011
Article in Oxford Textbook Med
MB Pepys et al.
Oxford Textbook Med 1995
Article in Lancet
Emerging Risk Factors Collaboration et al.
Lancet 2010
Article in J Clin Investig
H Xu et al.
J Clin Investig 2003
Article in Circulation
A Dehghan et al.
Circulation 2011
Article in Nat Rev Genet
PA Jones et al.
Nat Rev Genet 2012
Article in Genet Epidemiol
RT Barfield et al.
Genet Epidemiol 2014
Article in Nature
V Hornung et al.
Nature 2009
Article in Cell Death Differ
F Martinon et al.
Cell Death Differ 2007
Article in Front Immunol
B Carow et al.
Front Immunol 2014

Similar Publications