Research Article

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

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Science  03 Aug 2018:
eaaq1327
DOI: 10.1126/science.aaq1327

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Abstract

Proteins circulating in the blood are critical for age-related disease processes, however the serum proteome has remained largely unexplored. To this end, 4,137 proteins covering most predicted extracellular proteins, were measured in the serum of 5,457 Icelanders over 65 years of age. Pair-wise 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.

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