小柯机器人

冰岛安进公司Kari Stefansson、Patrick Sulem研究小组在研究中取得进展。他们对血浆蛋白质组与遗传学和疾病的关系进行了大规模整合。相关论文于2021年12月2日发表在《自然-遗传学》杂志上。

在本研究中，研究人员在35,559名冰岛人中对4,907个适体测量的血浆蛋白水平进行了全基因组关联研究(GWAS)。研究揭示了18,084个序列变异与血浆蛋白质水平（蛋白质数量性状基因座；pQTL）之间的关联，其中19%具有罕见变异（次要等位基因频率(MAF) < 1%）。研究测试了血浆蛋白水平与373种疾病和其他特征的关联，并确定了257,490种关联。

研究人员将pQTL和遗传关联与疾病和其他性状相结合，发现GWAS目录中45,334个先导关联中有12%与pQTL存在高度连锁不平衡变异。研究鉴定了938个编码潜在药物靶点的基因，这些基因具有影响可能生物标志物水平的变体。通过将蛋白质组学、基因组学和转录组学相结合，该研究提供了一种宝贵的资源，可用于提高对疾病发病机制的了解并协助药物发现和研发。

据了解，血浆蛋白质组可以测量基因组与疾病发生之间的概率。

附：英文原文

Title: Large-scale integration of the plasma proteome with genetics and disease

Author: Ferkingstad, Egil, Sulem, Patrick, Atlason, Bjarni A., Sveinbjornsson, Gardar, Magnusson, Magnus I., Styrmisdottir, Edda L., Gunnarsdottir, Kristbjorg, Helgason, Agnar, Oddsson, Asmundur, Halldorsson, Bjarni V., Jensson, Brynjar O., Zink, Florian, Halldorsson, Gisli H., Masson, Gisli, Arnadottir, Gudny A., Katrinardottir, Hildigunnur, Juliusson, Kristinn, Magnusson, Magnus K., Magnusson, Olafur Th., Fridriksdottir, Run, Saevarsdottir, Saedis, Gudjonsson, Sigurjon A., Stacey, Simon N., Rognvaldsson, Solvi, Eiriksdottir, Thjodbjorg, Olafsdottir, Thorunn A., Steinthorsdottir, Valgerdur, Tragante, Vinicius, Ulfarsson, Magnus O., Stefansson, Hreinn, Jonsdottir, Ingileif, Holm, Hilma, Rafnar, Thorunn, Melsted, Pall, Saemundsdottir, Jona, Norddahl, Gudmundur L., Lund, Sigrun H., Gudbjartsson, Daniel F., Thorsteinsdottir, Unnur, Stefansson, Kari

Issue&Volume: 2021-12-02

Abstract: The plasma proteome can help bridge the gap between the genome and diseases. Here we describe genome-wide association studies (GWASs) of plasma protein levels measured with 4,907 aptamers in 35,559 Icelanders. We found 18,084 associations between sequence variants and levels of proteins in plasma (protein quantitative trait loci; pQTL), of which 19% were with rare variants (minor allele frequency (MAF)<1%). We tested plasma protein levels for association with 373 diseases and other traits and identified 257,490 associations. We integrated pQTL and genetic associations with diseases and other traits and found that 12% of 45,334 lead associations in the GWAS Catalog are with variants in high linkage disequilibrium with pQTL. We identified 938 genes encoding potential drug targets with variants that influence levels of possible biomarkers. Combining proteomics, genomics and transcriptomics, we provide a valuable resource that can be used to improve understanding of disease pathogenesis and to assist with drug discovery and development.

DOI: 10.1038/s41588-021-00978-w

Source: https://www.nature.com/articles/s41588-021-00978-w

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