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

<p dir="ltr">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 pop...

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Main Author: Shaza B. Zaghlool (10836602) (author)
Other Authors: Brigitte Kühnel (3342752) (author), Mohamed A. Elhadad (9321662) (author), Sara Kader (14152683) (author), Anna Halama (545988) (author), Gaurav Thareja (459188) (author), Rudolf Engelke (1754893) (author), Hina Sarwath (4480654) (author), Eman K. Al-Dous (14152686) (author), Yasmin A. Mohamoud (10671696) (author), Thomas Meitinger (26605) (author), Rory Wilson (332489) (author), Konstantin Strauch (73658) (author), Annette Peters (62601) (author), Dennis O. Mook-Kanamori (148319) (author), Johannes Graumann (1297758) (author), Joel A. Malek (10327973) (author), Christian Gieger (87555) (author), Melanie Waldenberger (236985) (author), Karsten Suhre (67967) (author)
Published: 2020
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author Shaza B. Zaghlool (10836602)
author2 Brigitte Kühnel (3342752)
Mohamed A. Elhadad (9321662)
Sara Kader (14152683)
Anna Halama (545988)
Gaurav Thareja (459188)
Rudolf Engelke (1754893)
Hina Sarwath (4480654)
Eman K. Al-Dous (14152686)
Yasmin A. Mohamoud (10671696)
Thomas Meitinger (26605)
Rory Wilson (332489)
Konstantin Strauch (73658)
Annette Peters (62601)
Dennis O. Mook-Kanamori (148319)
Johannes Graumann (1297758)
Joel A. Malek (10327973)
Christian Gieger (87555)
Melanie Waldenberger (236985)
Karsten Suhre (67967)
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author_facet Shaza B. Zaghlool (10836602)
Brigitte Kühnel (3342752)
Mohamed A. Elhadad (9321662)
Sara Kader (14152683)
Anna Halama (545988)
Gaurav Thareja (459188)
Rudolf Engelke (1754893)
Hina Sarwath (4480654)
Eman K. Al-Dous (14152686)
Yasmin A. Mohamoud (10671696)
Thomas Meitinger (26605)
Rory Wilson (332489)
Konstantin Strauch (73658)
Annette Peters (62601)
Dennis O. Mook-Kanamori (148319)
Johannes Graumann (1297758)
Joel A. Malek (10327973)
Christian Gieger (87555)
Melanie Waldenberger (236985)
Karsten Suhre (67967)
author_role author
dc.creator.none.fl_str_mv Shaza B. Zaghlool (10836602)
Brigitte Kühnel (3342752)
Mohamed A. Elhadad (9321662)
Sara Kader (14152683)
Anna Halama (545988)
Gaurav Thareja (459188)
Rudolf Engelke (1754893)
Hina Sarwath (4480654)
Eman K. Al-Dous (14152686)
Yasmin A. Mohamoud (10671696)
Thomas Meitinger (26605)
Rory Wilson (332489)
Konstantin Strauch (73658)
Annette Peters (62601)
Dennis O. Mook-Kanamori (148319)
Johannes Graumann (1297758)
Joel A. Malek (10327973)
Christian Gieger (87555)
Melanie Waldenberger (236985)
Karsten Suhre (67967)
dc.date.none.fl_str_mv 2020-01-03T21:00:00Z
dc.identifier.none.fl_str_mv 10.1038/s41467-019-13831-w
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Epigenetics_meets_proteomics_in_an_epigenome-wide_association_study_with_circulating_blood_plasma_protein_traits/21598071
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Biochemistry and cell biology
Genetics
Biomedical and clinical sciences
Oncology and carcinogenesis
Prostate Cancer (PC)
Castration-Resistant Prostate Cancer
Neuroendocrine Prostate Cancer (NEPC)
miR-708
Apoptosis
Tumor Xenografts
dc.title.none.fl_str_mv Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">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 <i>NLRC5</i>, 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.</p><h2>Other Information</h2><p dir="ltr">Published in: Nature Communications<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1038/s41467-019-13831-w" target="_blank">http://dx.doi.org/10.1038/s41467-019-13831-w</a></p>
eu_rights_str_mv openAccess
id Manara2_8bbc6336abd29fc0efa6f89715a0ad8f
identifier_str_mv 10.1038/s41467-019-13831-w
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/21598071
publishDate 2020
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rights_invalid_str_mv CC BY 4.0
spelling Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traitsShaza B. Zaghlool (10836602)Brigitte Kühnel (3342752)Mohamed A. Elhadad (9321662)Sara Kader (14152683)Anna Halama (545988)Gaurav Thareja (459188)Rudolf Engelke (1754893)Hina Sarwath (4480654)Eman K. Al-Dous (14152686)Yasmin A. Mohamoud (10671696)Thomas Meitinger (26605)Rory Wilson (332489)Konstantin Strauch (73658)Annette Peters (62601)Dennis O. Mook-Kanamori (148319)Johannes Graumann (1297758)Joel A. Malek (10327973)Christian Gieger (87555)Melanie Waldenberger (236985)Karsten Suhre (67967)Biological sciencesBiochemistry and cell biologyGeneticsBiomedical and clinical sciencesOncology and carcinogenesisProstate Cancer (PC)Castration-Resistant Prostate CancerNeuroendocrine Prostate Cancer (NEPC)miR-708ApoptosisTumor Xenografts<p dir="ltr">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 <i>NLRC5</i>, 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.</p><h2>Other Information</h2><p dir="ltr">Published in: Nature Communications<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1038/s41467-019-13831-w" target="_blank">http://dx.doi.org/10.1038/s41467-019-13831-w</a></p>2020-01-03T21:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41467-019-13831-whttps://figshare.com/articles/journal_contribution/Epigenetics_meets_proteomics_in_an_epigenome-wide_association_study_with_circulating_blood_plasma_protein_traits/21598071CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/215980712020-01-03T21:00:00Z
spellingShingle Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits
Shaza B. Zaghlool (10836602)
Biological sciences
Biochemistry and cell biology
Genetics
Biomedical and clinical sciences
Oncology and carcinogenesis
Prostate Cancer (PC)
Castration-Resistant Prostate Cancer
Neuroendocrine Prostate Cancer (NEPC)
miR-708
Apoptosis
Tumor Xenografts
status_str publishedVersion
title Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits
title_full Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits
title_fullStr Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits
title_full_unstemmed Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits
title_short Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits
title_sort Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits
topic Biological sciences
Biochemistry and cell biology
Genetics
Biomedical and clinical sciences
Oncology and carcinogenesis
Prostate Cancer (PC)
Castration-Resistant Prostate Cancer
Neuroendocrine Prostate Cancer (NEPC)
miR-708
Apoptosis
Tumor Xenografts