Co-regulatory networks of human serum proteins link genetics to disease

作者：Valur Emilsson, Marjan Ilkov, John R. Lamb, Nancy Finkel, Elías F. Guðmundsson, Rebecca Pitts, Heather Hoover, Valborg Guðmundsdóttir, Shane R. Horman, Thor Aspelund, Le Shu, Vladimir Trifonov, Sigurður Sigurðsson, Andrei Manolescu, Jun Zhu, Ö Ólafsson, Jóhanna Jakobsdóttir, Scott A. Lesley, Jeremy To, Jia Zhang, Tamara B. Harris, Lenore J. Launer, Bin Zhang, Guðný Eiríksdóttir, Xia Yang, Anthony P. Orth, Lori L. Jennings, Vilmundur Guðnason · 发表于：Science · 年份：2018 · DOI：10.1126/science.aaq1327 · 被引用次数：746 · 研究领域：Bioinformatics and Genomic Networks、Genetic Associations and Epidemiology、Advanced Proteomics Techniques and Applications

Proteins circulating in the blood are critical for age-related disease processes; however, the serum proteome has remained largely unexplored. To this end, 4137 proteins covering most predicted extracellular proteins were measured in the serum of 5457 Icelanders over 65 years of age. Pairwise correlation between proteins as they varied across individuals revealed 27 different network modules of serum proteins, many of which were associated with cardiovascular and metabolic disease states, as well as overall survival. The protein modules were controlled by cis- and trans-acting genetic variants, which in many cases were also associated with complex disease. This revealed co-regulated groups of circulating proteins that incorporated regulatory control between tissues and demonstrated close relationships to past, current, and future disease states.