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 and Karsten Suhre ()
Additional contact information
Shaza B. Zaghlool: Weill Cornell Medicine-Qatar
Brigitte Kühnel: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
Mohamed A. Elhadad: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
Sara Kader: Weill Cornell Medicine-Qatar
Anna Halama: Weill Cornell Medicine-Qatar
Gaurav Thareja: Weill Cornell Medicine-Qatar
Rudolf Engelke: Proteomics Core, Weill Cornell Medicine‐Qatar
Hina Sarwath: Proteomics Core, Weill Cornell Medicine‐Qatar
Eman K. Al-Dous: Genomics Core, Weill Cornell Medicine-Qatar
Yasmin A. Mohamoud: Genomics Core, Weill Cornell Medicine-Qatar
Thomas Meitinger: German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance
Rory Wilson: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
Konstantin Strauch: Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
Annette Peters: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
Dennis O. Mook-Kanamori: Department of Clinical Epidemiology, Leiden University Medical Centre
Johannes Graumann: Scientific Service Group Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, W.G. Kerckhoff Institute
Joel A. Malek: Genomics Core, Weill Cornell Medicine-Qatar
Christian Gieger: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
Melanie Waldenberger: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
Karsten Suhre: Weill Cornell Medicine-Qatar

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-019-13831-w

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