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Zaghlool, S.B.* ; Sharma, S. ; Molnar, M. ; Matias-Garcia, P.R. ; Elhadad, M.A. ; Waldenberger, M. ; Peters, A. ; Rathmann, W.* ; Graumann, J.* ; Gieger, C. ; Grallert, H. ; Suhre, K.*

Revealing the role of the human blood plasma proteome in obesity using genetic drivers.

Nat. Commun. 12:1279 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold
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Blood circulating proteins are confounded readouts of the biological processes that occur in different tissues and organs. Many proteins have been linked to complex disorders and are also under substantial genetic control. Here, we investigate the associations between over 1000 blood circulating proteins and body mass index (BMI) in three studies including over 4600 participants. We show that BMI is associated with widespread changes in the plasma proteome. We observe 152 replicated protein associations with BMI. 24 proteins also associate with a genome-wide polygenic score (GPS) for BMI. These proteins are involved in lipid metabolism and inflammatory pathways impacting clinically relevant pathways of adiposity. Mendelian randomization suggests a bi-directional causal relationship of BMI with LEPR/LEP, IGFBP1, and WFIKKN2, a protein-to-BMI relationship for AGER, DPT, and CTSA, and a BMI-to-protein relationship for another 21 proteins. Combined with animal model and tissue-specific gene expression data, our findings suggest potential therapeutic targets further elucidating the role of these proteins in obesity associated pathologies.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 12, Issue: 1, Pages: , Article Number: 1279 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Grants Münchner Zentrum für Gesundheitswissenschaften, Ludwig-Maximilians-Universität München
Deutsches Forschungszentrum für Gesundheit und Umwelt, Helmholtz Zentrum München
Bundesministerium für Bildung und Forschung
Qatar National Research Fund (Qatar Foundation)
National Institute of Neurological Disorders and Stroke
National Cancer Institute
National Human Genome Research Institute
National Heart, Lung, and Blood Institute
National Institute on Drug Abuse
National Institute of Mental Health