A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation.

Details

Serval ID
serval:BIB_E8D5336A9032
Type
Article: article from journal or magazin.
Collection
Publications
Title
A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation.
Journal
PLoS genetics
Author(s)
Naitza S., Porcu E., Steri M., Taub D.D., Mulas A., Xiao X., Strait J., Dei M., Lai S., Busonero F., Maschio A., Usala G., Zoledziewska M., Sidore C., Zara I., Pitzalis M., Loi A., Virdis F., Piras R., Deidda F., Whalen M.B., Crisponi L., Concas A., Podda C., Uzzau S., Scheet P., Longo D.L., Lakatta E., Abecasis G.R., Cao A., Schlessinger D., Uda M., Sanna S., Cucca F.
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Publication state
Published
Issued date
01/2012
Peer-reviewed
Oui
Volume
8
Number
1
Pages
e1002480
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
Publication Status: ppublish
Abstract
Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the mechanisms underlying this process. We first conducted a two-stage genome-wide association scan (GWAS) for the key inflammatory biomarkers Interleukin-6 (IL-6), the general measure of inflammation erythrocyte sedimentation rate (ESR), monocyte chemotactic protein-1 (MCP-1), and high-sensitivity C-reactive protein (hsCRP) in a large cohort of individuals from the founder population of Sardinia. By analysing 731,213 autosomal or X chromosome SNPs and an additional ∼1.9 million imputed variants in 4,694 individuals, we identified several SNPs associated with the selected quantitative trait loci (QTLs) and replicated all the top signals in an independent sample of 1,392 individuals from the same population. Next, to increase power to detect and resolve associations, we further genotyped the whole cohort (6,145 individuals) for 293,875 variants included on the ImmunoChip and MetaboChip custom arrays. Overall, our combined approach led to the identification of 9 genome-wide significant novel independent signals-5 of which were identified only with the custom arrays-and provided confirmatory evidence for an additional 7. Novel signals include: for IL-6, in the ABO gene (rs657152, p = 2.13×10(-29)); for ESR, at the HBB (rs4910472, p = 2.31×10(-11)) and UCN119B/SPPL3 (rs11829037, p = 8.91×10(-10)) loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53×10(-13)) and in CADM3 (rs3026968, p = 7.63×10(-13)); for hsCRP, within the CRP gene (rs3093077, p = 5.73×10(-21)), near DARC (rs3845624, p = 1.43×10(-10)), UNC119B/SPPL3 (rs11829037, p = 1.50×10(-14)), and ICOSLG/AIRE (rs113459440, p = 1.54×10(-08)) loci. Confirmatory evidence was found for IL-6 in the IL-6R gene (rs4129267); for ESR at CR1 (rs12567990) and TMEM57 (rs10903129); for MCP-1 at DARC (rs12075); and for hsCRP at CRP (rs1205), HNF1A (rs225918), and APOC-I (rs4420638). Our results improve the current knowledge of genetic variants underlying inflammation and provide novel clues for the understanding of the molecular mechanisms regulating this complex process.
Keywords
Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Blood Sedimentation, C-Reactive Protein/genetics, Chemokine CCL2/genetics, Female, Genome-Wide Association Study/methods, Humans, Inflammation/genetics, Interleukin-6/genetics, Italy, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci/genetics
Pubmed
Web of science
Open Access
Yes
Create date
18/01/2021 21:49
Last modification date
19/01/2021 6:26
Usage data