英国剑桥大学临床医学院Claudia Langenberg研究团队绘制了人类疾病的蛋白质-基因组融合图谱。该研究于2021年10月14日发表于国际一流学术期刊《科学》杂志上。

他们确定了 3,892 种血浆蛋白的 10,674 个遗传关联，以创建 1,859 个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融合。该蛋白质基因组图谱提供了一个框架，用于 1) 将病因相关的疾病联系起来，2) 为新出现的疾病提供生物学背景，以及 3) 整合不同的生物学域以建立已知基因-疾病联系的机制。他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，并建立了顺式蛋白质变异体在 GWAS 基因座上注释可能的致病基因的价值，解决了遗传发现的实验验证和临床转化的主要障碍。

研究人员表示，蛋白质遗传调控的表征对于了解疾病病因和开发治疗方法至关重要。

附：英文原文

Title: Mapping the proteo-genomic convergence of human diseases

Author: Maik Pietzner, Eleanor Wheeler, Julia Carrasco-Zanini, Adrian Cortes, Mine Koprulu, Maria A. Wrheide, Erin Oerton, James Cook, Isobel D. Stewart, Nicola D. Kerrison, Jian’an Luan, Johannes Raffler, Matthias Arnold, Wiebke Arlt, Stephen O’Rahilly, Gabi Kastenmüller, Eric R. Gamazon, Aroon D. Hingorani, Robert A. Scott, Nicholas J. Wareham, Claudia Langenberg

Issue&Volume: 2021-10-14

Abstract: 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.

DOI: abj1541

Source: https://www.science.org/doi/10.1126/science.abj1541