% pubman genre = article
@article{item_3634991,
title = {{Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease}},
author = {Yoshiji, Satoshi and Lu, Tianyuan and Butler-Laporte, Guillaume and Carrasco-Zanini-Sanchez, Julia and Su, Chen-Yang and Chen, Yiheng and Liang, Kevin and Willett, Julian Daniel Sunday and Wang, Shidong and Adra, Darin and Ilboudo, Yann and Sasako, Takayoshi and Koyama, Satoshi and Nakao, Tetsushi and Forgetta, Vincenzo and Farjoun, Yossi and Zeberg, Hugo and Zhou, Sirui and Marks-Hultstr{\"o}m, Michael and Machiela, Mitchell J. and Kaalia, Rama and Dashti, Hesam and Claussnitzer, Melina and Flannick, Jason and Wareham, Nicholas J. and Mooser, Vincent and Timpson, Nicholas J. and Langenberg, Claudia and Richards, J. Brent},
language = {eng},
issn = {1061-4036},
doi = {10.1038/s41588-024-02052-7},
publisher = {Nature America, Inc.},
address = {New York, NY},
year = {2025},
date = {2025-02},
abstract = {{Obesity strongly increases the risk of cardiometabolic diseases, yet the {\textless}br{\textgreater}underlying mediators of this relationship are not fully understood. Given that {\textless}br{\textgreater}obesity strongly influences circulating protein levels, we investigated proteins {\textless}br{\textgreater}mediating the effects of obesity on coronary artery disease, stroke and type 2 {\textless}br{\textgreater}diabetes. By integrating two-step proteome-wide Mendelian randomization, {\textless}br{\textgreater}colocalization, epigenomics and single-cell RNA sequencing, we identified {\textless}br{\textgreater}five mediators and prioritized collagen type VI $\alpha$3 (COL6A3). COL6A3 levels {\textless}br{\textgreater}were strongly increased by body mass index and increased coronary artery {\textless}br{\textgreater}disease risk. Notably, the carboxyl terminus product of COL6A3, endotrophin, {\textless}br{\textgreater}drove this effect. COL6A3 was highly expressed in disease-relevant cell types {\textless}br{\textgreater}and tissues. Finally, we found that body fat reduction could reduce plasma {\textless}br{\textgreater}levels of COL6A3-derived endotrophin, indicating a tractable way to modify {\textless}br{\textgreater}endotrophin levels. In summary, we provide actionable insights into how {\textless}br{\textgreater}circulating proteins mediate the effects of obesity on cardiometabolic {\textless}br{\textgreater}diseases and prioritize endotrophin as a potential therapeutic target.}},
journal = {{Nature Genetics}},
volume = {57},
number = {2},
pages = {345--357},
}