Institute of Translational Genomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Anogia Medical Centre, Anogia, Greece.
Mol Metab. 2023 Dec;78:101810. doi: 10.1016/j.molmet.2023.101810. Epub 2023 Sep 29.
Global cardiometabolic disease prevalence has grown rapidly over the years, making it the leading cause of death worldwide. Proteins are crucial components in biological pathways dysregulated in disease states. Identifying genetic components that influence circulating protein levels may lead to the discovery of biomarkers for early stages of disease or offer opportunities as therapeutic targets.
Here, we carry out a genome-wide association study (GWAS) utilising whole genome sequencing data in 3,005 individuals from the HELIC founder populations cohort, across 92 proteins of cardiometabolic relevance.
We report 322 protein quantitative trait loci (pQTL) signals across 92 proteins, of which 76 are located in or near the coding gene (cis-pQTL). We link those association signals with changes in protein expression and cardiometabolic disease risk using colocalisation and Mendelian randomisation (MR) analyses.
The majority of previously unknown signals we describe point to proteins or protein interactions involved in inflammation and immune response, providing genetic evidence for the contributing role of inflammation in cardiometabolic disease processes.
多年来，全球心血管代谢疾病的患病率迅速增长，使其成为全球主要死因。蛋白质是疾病状态下失调的生物途径的关键组成部分。鉴定影响循环蛋白水平的遗传成分可能会发现疾病早期的生物标志物，或为治疗靶点提供机会。
在这里，我们利用来自 HELIC 创始人群体队列的 3005 个人的全基因组测序数据，对 92 种与心血管代谢相关的蛋白质进行全基因组关联研究 (GWAS)。
我们报告了 92 种蛋白质中的 322 个蛋白质数量性状基因座 (pQTL) 信号，其中 76 个位于或靠近编码基因（顺式-pQTL）。我们使用共定位和孟德尔随机化 (MR) 分析将这些关联信号与蛋白质表达变化和心血管代谢疾病风险联系起来。
我们描述的大多数以前未知的信号指向参与炎症和免疫反应的蛋白质或蛋白质相互作用，为炎症在心血管代谢疾病过程中的作用提供了遗传证据。
