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

Wang, Yunpeng ; Nudel, Ron ; Benros, Michael E. ; Skogstrand, Kristin ; Fishilevich, Simon ; Lancet, Doron ; Sun, Jiangming LU orcid ; Hougaard, David M. ; Andreassen, Ole A. and Mortensen, Preben Bo , et al. (2020) In PLoS Genetics 16(11).
Abstract

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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Genetics
volume
16
issue
11
article number
e1009163
pages
19 pages
publisher
Public Library of Science (PLoS)
external identifiers
  • scopus:85097125948
  • pmid:33227023
ISSN
1553-7390
DOI
10.1371/journal.pgen.1009163
language
English
LU publication?
no
additional info
Funding Information: This study was supported by The Lundbeck Foundation (grant numbers R102-A9118, R155-2014-1724 and R268-2016-3925 and 278-2018-1411), Denmark, the Independent Research Fund Denmark (grant number 7025-00078B), the Stanley Medical Research Institute, an Advanced Grant from the European Research Council (project number 294838) and the Stanley Center for Psychiatric Research at Broad Institute and Centre for Integrated Register-based Research at Aarhus University (MEB,KS, iPSYCH-BROAD, DMH,PBM, TFH, and TW). WKT was in part supported by NIH grant R01GM104400. DL and SF were supported by a grant from LifeMap Sciences Inc. (Calfornia, USA). This research has been conducted using the Danish National Biobank resource, supported by the Novo Nordisk Foundation (SK and DMH). YW and OAA are supported by the Research Council of Norway (Dr. Wang through a FRIPRO Young Talented Grant (#302854) and a FRIPRO Mobility grant scheme (#251134)) and the UiO:Life Science Convergence Environment (4MENT). The FRIPRO Mobility grant scheme (FRICON) is co-funded by the European Union's Seventh Framework Programme for research, technological development and demonstration under Marie Curie grant agreement No. 608695. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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.
id
77c5568d-ee1f-4eb1-b212-c7a3b52c673a
date added to LUP
2022-03-22 11:14:37
date last changed
2024-06-21 02:59:03
@article{77c5568d-ee1f-4eb1-b212-c7a3b52c673a,
  abstract     = {{<p>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 &lt; 5 x 10<sup>−9</sup>), 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.</p>}},
  author       = {{Wang, Yunpeng and Nudel, Ron and Benros, Michael E. and Skogstrand, Kristin and Fishilevich, Simon and Lancet, Doron and Sun, Jiangming and Hougaard, David M. and Andreassen, Ole A. and Mortensen, Preben Bo and Buil, Alfonso and Hansen, Thomas F. and Thompson, Wesley K. and Werge, Thomas}},
  issn         = {{1553-7390}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{11}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS Genetics}},
  title        = {{Genome-wide association study identifies 16 genomic regions associated with circulating cytokines at birth}},
  url          = {{http://dx.doi.org/10.1371/journal.pgen.1009163}},
  doi          = {{10.1371/journal.pgen.1009163}},
  volume       = {{16}},
  year         = {{2020}},
}