Analysis of repeated leukocyte DNA methylation assessments reveals persistent epigenetic alterations after an incident myocardial infarction
Posted on 2018-12-27 - 05:00
Abstract Background Most research into myocardial infarctions (MIs) have focused on preventative efforts. For survivors, the occurrence of an MI represents a major clinical event that can have long-lasting consequences. There has been little to no research into the molecular changes that can occur as a result of an incident MI. Here, we use three cohorts to identify epigenetic changes that are indicative of an incident MI and their association with gene expression and metabolomics. Results Using paired samples from the KORA cohort, we screened for DNA methylation loci (CpGs) whose change in methylation is potentially indicative of the occurrence of an incident MI between the baseline and follow-up exams. We used paired samples from the NAS cohort to identify 11 CpGs which were predictive in an independent cohort. After removing two CpGs associated with medication usage, we were left with an “epigenetic fingerprint” of MI composed of nine CpGs. We tested this fingerprint in the InCHIANTI cohort where it moderately discriminated incident MI occurrence (AUC = 0.61, P = 6.5 × 10−3). Returning to KORA, we associated the epigenetic fingerprint loci with cis-gene expression and integrated it into a gene expression-metabolomic network, which revealed links between the epigenetic fingerprint CpGs and branched chain amino acid (BCAA) metabolism. Conclusions There are significant changes in DNA methylation after an incident MI. Nine of these CpGs show consistent changes in multiple cohorts, significantly discriminate MI in independent cohorts, and were independent of medication usage. Integration with gene expression and metabolomics data indicates a link between MI-associated epigenetic changes and BCAA metabolism.
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Ward-Caviness, Cavin; Agha, Golareh; Chen, Brian; Pfeiffer, Liliane; Wilson, Rory; Wolf, Petra; et al. (2018). Analysis of repeated leukocyte DNA methylation assessments reveals persistent epigenetic alterations after an incident myocardial infarction. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4348475.v1
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AUTHORS (21)
CW
Cavin Ward-Caviness
GA
Golareh Agha
BC
Brian Chen
LP
Liliane Pfeiffer
RW
Rory Wilson
PW
Petra Wolf
CG
Christian Gieger
JS
Joel Schwartz
PV
Pantel Vokonas
LH
Lifang Hou
AJ
Allan Just
SB
Stefania Bandinelli
DH
Dena Hernandez
AS
Andrew Singleton
HP
Holger Prokisch
TM
Thomas Meitinger
GK
Gabi Kastenmüller
LF
Luigi Ferrucci
AB
Andrea Baccarelli
MW
Melanie Waldenberger