Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Sci Rep. 2024 Apr 2;14(1):7694. doi: 10.1038/s41598-024-57966-3.
The proteome holds great potential as an intermediate layer between the genome and phenome. Previous protein quantitative trait locus studies have focused mainly on describing the effects of common genetic variations on the proteome. Here, we assessed the impact of the common and rare genetic variations as well as the copy number variants (CNVs) on 326 plasma proteins measured in up to 500 individuals. We identified 184 cis and 94 trans signals for 157 protein traits, which were further fine-mapped to credible sets for 101 cis and 87 trans signals for 151 proteins. Rare genetic variation contributed to the levels of 7 proteins, with 5 cis and 14 trans associations. CNVs were associated with the levels of 11 proteins (7 cis and 5 trans), examples including a 3q12.1 deletion acting as a hub for multiple trans associations; and a CNV overlapping NAIP, a sensor component of the NAIP-NLRC4 inflammasome which is affecting pro-inflammatory cytokine interleukin 18 levels. In summary, this work presents a comprehensive resource of genetic variation affecting the plasma protein levels and provides the interpretation of identified effects.
蛋白质组作为基因组和表型之间的中间层具有巨大的潜力。之前的蛋白质数量性状基因座研究主要集中在描述常见遗传变异对蛋白质组的影响。在这里，我们评估了常见和罕见遗传变异以及拷贝数变异（CNV）对多达 500 个人的 326 种血浆蛋白的影响。我们鉴定了 157 种蛋白质特征的 184 个顺式和 94 个反式信号，进一步对 101 个顺式和 87 个反式信号进行了精细映射，得到了 151 种蛋白质的可信集合。罕见遗传变异导致了 7 种蛋白质的水平发生变化，其中 5 种是顺式关联，14 种是反式关联。CNV 与 11 种蛋白质的水平有关（7 个顺式和 5 个反式），例如 3q12.1 缺失作为多个反式关联的枢纽；以及一个重叠了 NAIP 的 CNV，NAIP 是 NAIP-NLRC4 炎症小体的传感器组件，影响促炎细胞因子白细胞介素 18 的水平。总之，这项工作提供了一个全面的遗传变异资源，影响了血浆蛋白水平，并对已识别的影响进行了解释。
