Revealing the role of the human blood plasma proteome in obesity using genetic drivers.
Revealing the role of the human blood plasma proteome in obesity using genetic drivers.
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DOI：
10.1038/s41467-021-21542-4
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发表时间：
2021-02-24
影响因子：
16.6
通讯作者：
Suhre K
中科院分区：
文献类型：
--
作者：
Zaghlool SB;Sharma S;Molnar M;Matías-García PR;Elhadad MA;Waldenberger M;Peters A;Rathmann W;Graumann J;Gieger C;Grallert H;Suhre K
血液循环蛋白是不同组织和器官中发生的生物过程的混杂读数。许多蛋白质与复杂的疾病有关，并且也受到大量遗传控制。在这里，我们在三项涉及 4600 多名参与者的研究中调查了 1000 多种血液循环蛋白与体重指数 (BMI) 之间的关联。我们发现体重指数与血浆蛋白质组的广泛变化有关。我们观察到 152 个与 BMI 相关的重复蛋白质。 24 种蛋白质还与 BMI 的全基因组多基因评分 (GPS) 相关。这些蛋白质参与脂质代谢和炎症途径，影响肥胖的临床相关途径。孟德尔随机化表明 BMI 与 LEPR/LEP、IGFBP1 和 WFIKKN2 存在双向因果关系，AGER、DPT 和 CTSA 存在蛋白质与 BMI 关系，以及另外 21 种蛋白质的 BMI 与蛋白质关系。结合动物模型和组织特异性基因表达数据，我们的研究结果表明潜在的治疗靶点进一步阐明了这些蛋白质在肥胖相关病理中的作用。血液循环蛋白质反映生物过程，从而提供对复杂特征的洞察。作者在此研究了 1000 种血浆蛋白与体重指数 (BMI) 之间的关系，强调了广泛的蛋白质组变化以及 BMI 与特定蛋白质之间的因果关系。
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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影响因子：
4.9
作者：
Garcia S;Hartkamp LM;Malvar-Fernandez B;van Es IE;Lin H;Wong J;Long L;Zanghi JA;Rankin AL;Masteller EL;Wong BR;Radstake TR;Tak PP;Reedquist KA
通讯作者：
Reedquist KA
影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
DOI：
10.1530/joe-11-0240
发表时间：
2011-12
期刊：
The Journal of endocrinology
影响因子：
--
作者：
Gray A;Aronson WJ;Barnard RJ;Mehta H;Wan J;Said J;Cohen P;Galet C
通讯作者：
Galet C
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
4.3
作者：
Ginsberg, Shira;Laron, Zvi;Vaisman, Nachum
通讯作者：
Vaisman, Nachum