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

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 pro...

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Veröffentlicht in:Nature communications Jg. 12; H. 1; S. 1279 - 13
Hauptverfasser: Zaghlool, Shaza B., Sharma, Sapna, Molnar, Megan, Matías-García, Pamela R., Elhadad, Mohamed A., Waldenberger, Melanie, Peters, Annette, Rathmann, Wolfgang, Graumann, Johannes, Gieger, Christian, Grallert, Harald, Suhre, Karsten
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 24.02.2021
Nature Publishing Group
Nature Portfolio
Schlagworte:
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45/43
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692/53/2423
692/699/1702/393
Adipose tissue
Adult
Aged
Animal models
Biological activity
Blood
Blood circulation
Blood plasma
Body Mass Index
Body size
Female
Gene expression
Genetic control
Genomes
Humanities and Social Sciences
Humans
Inflammation
Insulin-like growth factor-binding protein 1
Lipid metabolism
Lipid Metabolism - genetics
Lipid Metabolism - physiology
Lipids
Male
Mendelian Randomization Analysis
Middle Aged
multidisciplinary
Obesity
Obesity - genetics
Obesity - metabolism
Organs
Plasma proteins
Polygenic inheritance
Proteins
Proteome - metabolism
Proteomes
Proteomics - methods
Science
Science (multidisciplinary)
Therapeutic targets
ISSN:2041-1723, 2041-1723
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Zusammenfassung: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. Blood circulating proteins reflect biological processes, thus providing insight into complex traits. Here the authors study the relationship between 1000 plasma proteins and body mass index (BMI), highlighting widespread proteome changes and causal relationships between BMI and specific proteins.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-21542-4