THU582 Actionable Circulating Proteins Mediate The Effect Of Obesity On Cardiometabolic Diseases: An Integrative Proteogenomics Analysis

Disclosure: S. Yoshiji: None. T. Lu: Employee; Self; 5 Prime Sciences. G. Butler-Laporte: None. J. Carrasco-Zanini-Sanchez: None. Y. Chen: None. K. Liang: None. J.D. Willett: None. C. Su: None. S. Wang: Employee; Self; SomaLogic. D. Adra: None. Y. Ilbudo: None. S. Takayoshi: None. V. Forgetta: None....

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Published in:Journal of the Endocrine Society 2023-10, Vol.7 (Supplement_1)
Main Authors: Yoshiji, Satoshi, Lu, Tianyuan, Butler-Laporte, Guillaume, Carrasco-Zanini-Sanchez, Julia, Chen, Yiheng, Liang, Kevin, Sunday Willett, Julian Daniel, Su, Chen-Yang, Wang, Shidong, Adra, Darin, Ilbudo, Yann, Takayoshi, Sasako, Forgetta, Vincenzo, Farjoun, Yossi, Zeberg, Hugo, Zhou, Sirui, Machiela, Mitchell, Hultstrom, Michael, Wareham, Nicholas, Timpson, Nicholas J, Mooser, Vincent, Langenberg, Claudia, Richards, Brent
Format: Article
Language:English
Subjects:
Cardiovascular Endocrinology
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Summary:Disclosure: S. Yoshiji: None. T. Lu: Employee; Self; 5 Prime Sciences. G. Butler-Laporte: None. J. Carrasco-Zanini-Sanchez: None. Y. Chen: None. K. Liang: None. J.D. Willett: None. C. Su: None. S. Wang: Employee; Self; SomaLogic. D. Adra: None. Y. Ilbudo: None. S. Takayoshi: None. V. Forgetta: None. Y. Farjoun: Employee; Self; Fulcrum Genomics. H. Zeberg: None. S. Zhou: None. M. Machiela: None. M. Hultstrom: None. N. Wareham: None. N.J. Timpson: None. V. Mooser: None. C. Langenberg: None. B. Richards: Advisory Board Member; Self; GlaxoSmithKline. Owner/Co-Owner; Self; 5 Prime Sciences. Background: Obesity strongly increases the risk of cardiometabolic diseases; however, the underlying mediators of this relationship are not fully understood. As obesity strongly influences the plasma proteome, one strategy to disentangle this relationship is to identify plasma proteins mediating this relationship in humans. Since plasma proteins can be measured and in some cases modulated, they may offer attractive therapeutic targets. Aims: To identify plasma proteins mediating the relationship between obesity and coronary artery disease, stroke, and type 2 diabetes using an integrative analysis of proteome-wide Mendelian randomization (MR), statistical colocalization, mediation analyses, and single-cell RNA sequencing. Results: We screened 4,907 plasma proteins to identify proteins influenced by body mass index (BMI) with MR, wherein we used genome-wide association studies in up to one million individuals to make causal inference. This identified 2,714 BMI-influenced proteins (false discovery rate
ISSN:2472-1972
2472-1972
DOI:10.1210/jendso/bvad114.580