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Genome-wide association study identifies 16 genomic regions associated with circulating cytokines at birth

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  • iPSYCH-BROAD
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Circulating inflammatory markers are essential to human health and disease, and they are often dysregulated or malfunctioning in cancers as well as in cardiovascular, metabolic, immunologic and neuropsychiatric disorders. However, the genetic contribution to the physiological variation of levels of circulating inflammatory markers is largely unknown. Here we report the results of a genome-wide genetic study of blood concentration of ten cytokines, including the hitherto unexplored calcium-binding protein (S100B). The study leverages a unique sample of neonatal blood spots from 9,459 Danish subjects from the iPSYCH initiative. We estimate the SNP-heritability of marker levels as ranging from essentially zero for Erythropoietin (EPO) up to 73% for S100B. We identify and replicate 16 associated genomic regions (p < 5 x 10 −9), of which four are novel. We show that the associated variants map to enhancer elements, suggesting a possible transcriptional effect of genomic variants on the cytokine levels. The identification of the genetic architecture underlying the basic levels of cytokines is likely to prompt studies investigating the relationship between cytokines and complex disease. Our results also suggest that the genetic architecture of cytokines is stable from neonatal to adult life.

Original languageEnglish
Article numbere1009163
JournalPlos Genetics
Volume16
Issue number11
Pages (from-to)e1009163
ISSN1553-7404
DOIs
Publication statusPublished - Nov 2020

Bibliographical note

Publisher Copyright:
© 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

    Research areas

  • Biomarkers/blood, Cohort Studies, Cytokines/blood, Denmark, Enhancer Elements, Genetic/genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Infant, Newborn, Inflammation/blood, Male, Polymorphism, Single Nucleotide, Quantitative Trait Loci, S100 Calcium Binding Protein beta Subunit/blood

ID: 61715527