Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits

Shaza B. Zaghlool, Brigitte Kühnel, Mohamed A. Elhadad, Sara Kader, Anna Halama, Gaurav Thareja, Rudolf Engelke, Hina Sarwath, Eman K. Al-Dous, Yasmin A. Mohamoud, Thomas Meitinger, Rory Wilson, Konstantin Strauch, Annette Peters, Dennis O. Mook-Kanamori, Johannes Graumann, Joel A. Malek, Christian Gieger, Melanie Waldenberger, Karsten Suhre

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


DNA methylation and blood circulating proteins have been associated with many complex disorders, but the underlying disease-causing mechanisms often remain unclear. Here, we report an epigenome-wide association study of 1123 proteins from 944 participants of the KORA population study and replication in a multi-ethnic cohort of 344 individuals. We identify 98 CpG-protein associations (pQTMs) at a stringent Bonferroni level of significance. Overlapping associations with transcriptomics, metabolomics, and clinical endpoints suggest implication of processes related to chronic low-grade inflammation, including a network involving methylation of NLRC5, a regulator of the inflammasome, and associated pQTMs implicating key proteins of the immune system, such as CD48, CD163, CXCL10, CXCL11, LAG3, FCGR3B, and B2M. Our study links DNA methylation to disease endpoints via intermediate proteomics phenotypes and identifies correlative networks that may eventually be targeted in a personalized approach of chronic low-grade inflammation.

Original languageEnglish
Article number15
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2020


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