The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide a detailed summary of this initiative, including technical and biological validations, insights into proteomic disease signatures, and prediction modelling for various demographic and health indicators. We present comprehensive protein quantitative trait locus (pQTL) mapping of 2,923 proteins that identifies 14,287 primary genetic associations, of which 81% are previously undescribed, alongside ancestry-specific pQTL mapping in non-European individuals. The study provides an updated characterization of the genetic architecture of the plasma proteome, contextualized with projected pQTL discovery rates as sample sizes and proteomic assay coverages increase over time. We offer extensive insights into trans pQTLs across multiple biological domains, highlight genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks, and illustrate long-range epistatic effects of ABO blood group and FUT2 secretor status on proteins with gastrointestinal tissue-enriched expression. We demonstrate the utility of these data for drug discovery by extending the genetic proxied effects of protein targets, such as PCSK9, on additional endpoints, and disentangle specific genes and proteins perturbed at loci associated with COVID-19 susceptibility. This public–private partnership provides the scientific community with an open-access proteomics resource of considerable breadth and depth to help to elucidate the biological mechanisms underlying proteo-genomic discoveries and accelerate the development of biomarkers, predictive models and therapeutics¹.

Pharma 蛋白质组学项目是一个竞争前生物制药联盟，对 54,219 名英国生物样本库参与者的血浆蛋白质组学特征进行了表征。在这里，我们提供了该计划的详细摘要，包括技术和生物学验证、对蛋白质组学疾病特征的见解以及各种人口统计和健康指标的预测模型。我们提出了 2,923 种蛋白质的综合蛋白质数量性状基因座 （pQTL） 定位，确定了 14,287 个主要遗传关联，其中 81% 以前未描述过，以及非欧洲个体的祖先特异性 pQTL 定位。该研究提供了血浆蛋白质组遗传结构的最新特征，随着样本量和蛋白质组学检测覆盖率的增加，预计的 pQTL 发现率是相关的。我们提供了对跨多个生物结构域的反式 pQTL 的广泛见解，突出了遗传对不同细胞因子和补体网络集合中配体-受体相互作用和通路扰动的影响，并说明了 ABO 血型和 FUT2 分泌体状态对胃肠道组织富集表达蛋白的远程上位效应。我们通过将蛋白质靶标（如 PCSK9）的遗传代理效应扩展到其他终点，并解开在 COVID-19 易感性相关基因座上扰动的特定基因和蛋白质，证明了这些数据在药物发现中的效用。 这种公私合作为科学界提供了相当广度和深度的开放获取蛋白质组学资源，以帮助阐明蛋白质基因组学发现背后的生物学机制，并加速生物标志物、预测模型和治疗方法的开发¹。