92种循环蛋白的蛋白质组学分析及其在心脏代谢疾病中的作用。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Corinne Carland, Grace Png, Anders Malarstig, Pik Fang Kho, Stefan Gustafsson, Karl Michaelsson, Lars Lind, Emmanouil Tsafantakis, Maria Karaleftheri, George Dedoussis, Anna Ramisch, Erin Macdonald-Dunlop, Lucija Klaric, Peter K Joshi, Yan Chen, Hanna M Björck, Per Eriksson, Julia Carrasco-Zanini, Eleanor Wheeler, Karsten Suhre, Arthur Gilly, Eleftheria Zeggini, Ana Viñuela, Emmanouil T Dermitzakis, James F Wilson, Claudia Langenberg, Gaurav Thareja, Anna Halama, Frank Schmidt, Daniela Zanetti, Themistocles Assimes
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引用次数: 0

摘要

背景:人血浆中含有多种循环蛋白。这些蛋白是疾病的重要临床生物标志物,也是可能的药物靶点。对循环蛋白的大规模基因组学研究可以确定导致相对蛋白质丰度的遗传变异。方法:我们对12个队列中22997名主要欧洲血统个体的常染色体全基因组关联研究进行了荟萃分析,以确定92种心脏代谢相关血浆蛋白的蛋白质数量性状位点(pQTL)。结果:我们鉴定出503个(337个顺式和166个反式)条件独立的pqtl,包括一些未在文献中报道的新变体。我们进行了性别分层分析,发现118个(23.5%)pqtl表现出性别异质性。效应方向保持不变,但在效应大小和显著性上存在差异。此外,我们用最近的基因注释了反式pqtl,并报告了合理的生物学关系。使用孟德尔随机化,我们确定了19种表型中18种蛋白质的因果关系,其中10种有额外的遗传共定位证据。我们强调了与一系列心脏代谢特征相关的蛋白质,包括血管生成素相关蛋白7 (ANGPTL7)和信号蛋白3F (SEMA3F)。结论:通过对蛋白质数量性状位点的大规模分析,我们提供了与血浆蛋白相关的常见变异的全面概述。我们强调可能的生物学关系,这可能作为进一步研究心脏代谢疾病可能的因果作用的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases.

Background: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance.

Methods: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins.

Results: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F).

Conclusion: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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