Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3,892 plasma proteins to create a cis-anchored gene-protein-disease map of 1,859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to 1) connect etiologically related diseases, 2) provide biological context for new or emerging disorders, and 3) integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at GWAS loci, addressing a major barrier for experimental validation and clinical translation of genetic discoveries.

中文翻译：

---

绘制人类疾病的蛋白质基因组趋同图

蛋白质遗传调控的表征对于理解疾病病因和开发疗法至关重要。我们确定了 3,892 种血浆蛋白的 10,674 种遗传关联，以创建 1,859 种连接的顺式锚定基因-蛋白质-疾病图谱，突出了强大的跨疾病生物学趋同性。该蛋白质基因组图提供了一个框架，用于 1) 连接病因学相关疾病，2) 为新出现的或正在出现的疾病提供生物学背景，以及 3) 整合不同的生物学领域以建立已知基因-疾病联系的机制。我们的结果确定了疾病内部和疾病之间的蛋白质基因组联系，并确定了顺式蛋白质变体在 GWAS 位点注释可能致病基因的价值，