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A Genome-Wide Association Scan on the Levels of Markers of Inflammation in Sardinians Reveals Associations That Underpin Its Complex Regulation

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dc.contributor.author Naitza, Silvia
dc.contributor.author Porcu, Eleonora
dc.contributor.author Steri, Maristella
dc.contributor.author Taub, Dennis Daniel
dc.contributor.author Mulas, Antonella
dc.contributor.author Xiao, Xiang
dc.contributor.author Strait, James
dc.contributor.author Dei, Mariano
dc.contributor.author Lai, Sandra
dc.contributor.author Busonero, Fabio
dc.contributor.author Maschio, Andrea
dc.contributor.author Usala, Gianluca
dc.contributor.author Zoledziewska, Magdalena
dc.contributor.author Sidore, Carlo
dc.contributor.author Zara, Ilenia
dc.contributor.author Pitzalis, Maristella
dc.contributor.author Loi, Alessia
dc.contributor.author Virdis, Francesca
dc.contributor.author Piras, Roberta
dc.contributor.author Deidda, Francesca
dc.contributor.author Whalen, Michael B.
dc.contributor.author Crisponi, Laura
dc.contributor.author Concas, Antonio
dc.contributor.author Podda, Carlo
dc.contributor.author Uzzau, Sergio
dc.contributor.author Scheet, Paul
dc.contributor.author Longo, Dan L.
dc.contributor.author Lakatta, Edward
dc.contributor.author Abecasis, Gonçalo
dc.contributor.author Cao, Antonio
dc.contributor.author Schlessinger, David
dc.contributor.author Uda, Manuela
dc.contributor.author Sanna, Serena
dc.contributor.author Cucca, Francesco
dc.date.accessioned 2014-12-16T13:38:27Z
dc.date.available 2014-12-16T13:38:27Z
dc.date.issued 2012-01-26
dc.identifier.issn 1553-7390
dc.identifier.uri http://hdl.handle.net/11050/1138
dc.description.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 = 2.13610229); for ESR, at the HBB (rs4910472, p = 2.31610211) and UCN119B/SPPL3 (rs11829037, p = 8.91610210) loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53610213) and in CADM3 (rs3026968, p = 7.63610213); for hsCRP, within the CRP gene (rs3093077, p = 5.73610221), near DARC (rs3845624, p = 1.43610210), UNC119B/SPPL3 (rs11829037, p = 1.50610214), and ICOSLG/AIRE (rs113459440, p = 1.54610208) 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. IT
dc.language.iso en IT
dc.publisher Public Library of Science IT
dc.relation.ispartof PLoS Genetics IT
dc.relation.ispartofseries 8;1
dc.rights Attribuzione - Non commerciale - Non opere derivate 3.0 Italia *
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/it/ *
dc.subject Genome-wide association scan (GWAS) IT
dc.subject pro-inflammatory molecules IT
dc.subject erythrocyte sedimentation rate (ESR) IT
dc.title A Genome-Wide Association Scan on the Levels of Markers of Inflammation in Sardinians Reveals Associations That Underpin Its Complex Regulation IT
dc.type Articolo IT
dc.description.status Pubblicato IT
dc.identifier.doi 10.1371/journal.pgen.1002480 IT
dc.subject.een-cordis EEN CORDIS::SCIENZE BIOLOGICHE ::Ricerca sul genoma ::Espressione genica, ricerca proteomica IT
dc.identifier.eissn 1553-7404

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Attribuzione - Non commerciale - Non opere derivate 3.0 Italia Attribuzione - Non commerciale - Non opere derivate 3.0 Italia