Coding and regulatory variants are associated with serum protein levels and disease

Valur Emilsson; Valborg Gudmundsdottir; Alexander Gudjonsson; Thorarinn Jonmundsson; Brynjolfur G Jonsson; Mohd A Karim; Marjan Ilkov; James R Staley; Elias F Gudmundsson; Lenore J Launer; Jan H Lindeman; Nicholas M Morton; Thor Aspelund; John R Lamb; Lori L Jennings; Vilmundur Gudnason

doi:10.1038/s41467-022-28081-6

Coding and regulatory variants are associated with serum protein levels and disease

Nat Commun. 2022 Jan 25;13(1):481. doi: 10.1038/s41467-022-28081-6.

Authors

Valur Emilsson^#^{1

2}, Valborg Gudmundsdottir^#³, Alexander Gudjonsson^#³, Thorarinn Jonmundsson⁴, Brynjolfur G Jonsson³, Mohd A Karim^{5

6}, Marjan Ilkov³, James R Staley⁷, Elias F Gudmundsson³, Lenore J Launer⁸, Jan H Lindeman⁹, Nicholas M Morton¹⁰, Thor Aspelund³, John R Lamb¹¹, Lori L Jennings¹², Vilmundur Gudnason^{13

14}

Affiliations

¹ Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Kopavogur, Iceland. valur@hjarta.is.
² Faculty of Medicine, University of Iceland, 101 Reykjavik, Reykjavík, Iceland. valur@hjarta.is.
³ Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Kopavogur, Iceland.
⁴ Faculty of Medicine, University of Iceland, 101 Reykjavik, Reykjavík, Iceland.
⁵ Wellcome Trust Sanger Institute, Welcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
⁶ Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SD, UK.
⁷ BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁸ Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, MD, 20892-9205, USA.
⁹ Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.
¹⁰ Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
¹¹ GNF Novartis, 10675 John Jay Hopkins Drive, San Diego, CA, 92121, USA.
¹² Novartis Institutes for Biomedical Research, 22 Windsor Street, Cambridge, MA, 02139, USA.
¹³ Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Kopavogur, Iceland. v.gudnason@hjarta.is.
¹⁴ Faculty of Medicine, University of Iceland, 101 Reykjavik, Reykjavík, Iceland. v.gudnason@hjarta.is.

^# Contributed equally.

Abstract

Circulating proteins can be used to diagnose and predict disease-related outcomes. A deep serum proteome survey recently revealed close associations between serum protein networks and common disease. In the current study, 54,469 low-frequency and common exome-array variants were compared to 4782 protein measurements in the serum of 5343 individuals from the AGES Reykjavik cohort. This analysis identifies a large number of serum proteins with genetic signatures overlapping those of many diseases. More specifically, using a study-wide significance threshold, we find that 2021 independent exome array variants are associated with serum levels of 1942 proteins. These variants reside in genetic loci shared by hundreds of complex disease traits, highlighting serum proteins' emerging role as biomarkers and potential causative agents of a wide range of diseases.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Blood Proteins / genetics*
Disease / classification
Disease / genetics*
Exome / genetics*
Female
Genetic Predisposition to Disease*
Genotype*
Humans
Iceland
Male
Polymorphism, Single Nucleotide*
Proteome / metabolism*

Substances

Blood Proteins
Proteome

Abstract

Publication types

MeSH terms

Substances

Grants and funding