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Nat Genet. 2018 Nov;50(11):1524-1532. doi: 10.1038/s41588-018-0224-7. Epub 2018 Sep 24.

Individual variations in cardiovascular-disease-related protein levels are driven by genetics and gut microbiome.

Author information

1
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
2
Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg, Russian Federation.
3
Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
4
Genomics Coordination Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
5
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
6
Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
7
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
8
Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
9
K.G. Jebsen Coeliac Disease Research Centre, Department of Immunology, University of Oslo, Oslo, Norway.
10
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. a.zhernakova@umcg.nl.
11
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. j.fu@umcg.nl.
12
Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. j.fu@umcg.nl.

Abstract

Despite a growing body of evidence, the role of the gut microbiome in cardiovascular diseases is still unclear. Here, we present a systems-genome-wide and metagenome-wide association study on plasma concentrations of 92 cardiovascular-disease-related proteins in the population cohort LifeLines-DEEP. We identified genetic components for 73 proteins and microbial associations for 41 proteins, of which 31 were associated to both. The genetic and microbial factors identified mostly exert additive effects and collectively explain up to 76.6% of inter-individual variation (17.5% on average). Genetics contribute most to concentrations of immune-related proteins, while the gut microbiome contributes most to proteins involved in metabolism and intestinal health. We found several host-microbe interactions that impact proteins involved in epithelial function, lipid metabolism, and central nervous system function. This study provides important evidence for a joint genetic and microbial effect in cardiovascular disease and provides directions for future applications in personalized medicine.

PMID:
30250126
PMCID:
PMC6241851
[Available on 2019-03-24]
DOI:
10.1038/s41588-018-0224-7

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