Coding and regulatory variants affect serum protein levels and common disease

Valur Emilsson; Valborg Guðmundsdóttir; Alexander Guðjónsson; Mohd Anisul Karim; Marjan Ilkov; James R. Staley; Elias Freyr Gudmundsson; Brynjolfur G. Jonsson; Lenore J. Launer; Jan H.N. Lindeman; Nicholas M. Morton; Thor Aspelund; John R. Lamb; Lori L. Jennings; Vilmundur G. Gudnason

doi:10.1101/2020.05.06.080440

GeneticsbioRxivMay 6, 2020

Preprint

Coding and regulatory variants affect serum protein levels and common disease

Valur Emilsson iD, Valborg Guðmundsdóttir iD, Alexander Guðjónsson iD, Mohd Anisul Karim iD, Marjan Ilkov iD, James R. Staley iD, Elias Freyr Gudmundsson iD, Brynjolfur G. Jonsson iD, Lenore J. Launer iD, Jan H.N. Lindeman iD, Nicholas M. Morton iD, Thor Aspelund iD, John R. Lamb iD, Lori L. Jennings iD, Vilmundur G. Gudnason iD

Abstract

Circulating proteins are prognostic for human outcomes including cancer, heart failure, brain trauma and brain amyloid plaque burden. A deep serum proteome survey recently revealed close associations of serum protein networks and common diseases. The present study reveals unprecedented number of individual serum proteins that overlap genetic signatures of diseases emanating from different tissues of the body. Here, 54,469 low-frequency and common exome-array variants were compared with 4782 protein measurements in the serum of 5343 individuals of the deeply annotated AGES Reykjavik cohort. Using a study-wide significant threshold, 2019 independent exome array variants affecting levels of 2135 serum proteins were identified. These variants overlapped genetic loci for hundreds of complex disease traits, emphasizing the emerging role for serum proteins as biomarkers of and potential causative agents of multiple diseases.

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