Genome-wide association study identifies 16 genomic regions associated with circulating cytokines at birth.
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
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
17
02
2020
accepted:
29
09
2020
revised:
07
12
2020
pubmed:
24
11
2020
medline:
7
1
2021
entrez:
23
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33227023
doi: 10.1371/journal.pgen.1009163
pii: PGENETICS-D-20-00241
pmc: PMC7721185
doi:
Substances chimiques
Biomarkers
0
Cytokines
0
S100 Calcium Binding Protein beta Subunit
0
S100B protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009163Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM104400
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Brain Behav Immun. 2020 Jun 11;:
pubmed: 32534018
Methods. 2012 Feb;56(2):204-12
pubmed: 22001645
Nat Genet. 2015 Jun;47(6):598-606
pubmed: 25938943
J Exerc Rehabil. 2018 Apr 26;14(2):168-174
pubmed: 29740548
Nature. 2014 Jul 24;511(7510):421-7
pubmed: 25056061
Nat Commun. 2017 Feb 27;8:14357
pubmed: 28240269
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
Eur J Hum Genet. 2019 Sep;27(9):1445-1455
pubmed: 30976114
Nat Rev Cancer. 2004 Jan;4(1):11-22
pubmed: 14708024
Nature. 2017 Feb 8;542(7640):177-185
pubmed: 28179656
Cancer Res. 2008 Jan 1;68(1):323-8
pubmed: 18172326
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
Brain Behav Immun. 2002 Oct;16(5):525-32
pubmed: 12401466
Bioinformatics. 2016 May 15;32(10):1493-501
pubmed: 26773131
Database (Oxford). 2017 Jan 1;2017:
pubmed: 28605766
Nat Genet. 2015 Mar;47(3):284-90
pubmed: 25642633
Genome Med. 2018 Feb 22;10(1):11
pubmed: 29471866
Curr Protoc Bioinformatics. 2016 Jun 20;54:1.30.1-1.30.33
pubmed: 27322403
Nat Genet. 2014 Jun;46(6):543-550
pubmed: 24816252
Br Med Bull. 2005 Feb 08;71:93-113
pubmed: 15701924
Nature. 2014 Mar 27;507(7493):455-461
pubmed: 24670763
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
Nat Genet. 2012 Jul 22;44(8):955-9
pubmed: 22820512
J Clin Invest. 2015 Jun;125(6):2228-33
pubmed: 25893595
Nat Rev Immunol. 2014 May;14(5):329-42
pubmed: 24751956
N Engl J Med. 2008 May 15;358(20):2148-59
pubmed: 18480207
Mol Psychiatry. 2013 May;18(5):540-2
pubmed: 23478746
Cell. 2016 Nov 17;167(5):1415-1429.e19
pubmed: 27863252
Lancet. 2005 Oct 22-28;366(9495):1484-98
pubmed: 16243094
J Neuroinflammation. 2013 Apr 01;10:43
pubmed: 23547920
Nature. 2015 Feb 19;518(7539):317-30
pubmed: 25693563
Transl Psychiatry. 2019 Oct 7;9(1):252
pubmed: 31591381
Trends Genet. 2006 Jun;22(6):306-13
pubmed: 16697071
Nature. 2012 Sep 6;489(7414):57-74
pubmed: 22955616
PLoS Genet. 2016 Feb 24;12(2):e1005874
pubmed: 26910538
Am J Hum Genet. 2017 Jan 5;100(1):40-50
pubmed: 27989323
Nucleic Acids Res. 2007 Jan;35(Database issue):D88-92
pubmed: 17130149
Nat Genet. 2012 Jan 29;44(3):269-76
pubmed: 22286219
Biol Psychiatry. 2015 Jan 1;77(1):36-42
pubmed: 25444161
Nucleic Acids Res. 2016 Jan 4;44(D1):D164-71
pubmed: 26438538
PLoS Genet. 2006 Dec;2(12):e190
pubmed: 17194218
Genome Biol. 2015 Mar 24;16:56
pubmed: 25887522
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
Clin Chem. 2005 Oct;51(10):1854-66
pubmed: 16081507
Int Anesthesiol Clin. 2007 Spring;45(2):27-37
pubmed: 17426506
Circulation. 2011 Feb 22;123(7):731-8
pubmed: 21300955
Mol Psychiatry. 2018 Jan;23(1):6-14
pubmed: 28924187
Bioinformatics. 2010 Sep 15;26(18):2336-7
pubmed: 20634204
Nat Commun. 2014 Sep 04;5:4757
pubmed: 25187353
Transl Psychiatry. 2019 Nov 11;9(1):283
pubmed: 31712607
Nat Methods. 2011 Dec 04;9(2):179-81
pubmed: 22138821