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

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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. (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1371/journal.pgen.1002480 (literal)
Alternative label
  • Naitza S, Porcu E, Steri M, Taub DD, 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 MB, Crisponi L, Concas A, Podda C, Uzzau S, Scheet P, Longo DL, Lakatta E, Abecasis GR, Cao A, Schlessinger D, Uda M, Sanna S, Cucca F. (2012)
    A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation.
    in PLOS genetics (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Naitza S, Porcu E, Steri M, Taub DD, 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 MB, Crisponi L, Concas A, Podda C, Uzzau S, Scheet P, Longo DL, Lakatta E, Abecasis GR, Cao A, Schlessinger D, Uda M, Sanna S, Cucca F. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266885/ (literal)
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  • ubMe (literal)
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  • 1Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy 2Intramural Research Program, National Institute on Aging, Baltimore, Maryland, United States of America 3University of Texas, MD Anderson Cancer Center, Department of Epidemiology, Houston, Texas, United States of America 4Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy 5Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America 6Center for Advanced Studies, Research, and Development in Sardinia (CRS4), AGCT Program, Parco Scientifico e tecnologico della Sardegna, Pula, Italy 7High Performance Computing and Network, CRS4, Parco Tecnologico della Sardegna, Pula, Italy 8Porto Conte Ricerche, Località Tramariglio, Alghero, Sassari, Italy FAS Center for Systems Biology, Harvard University, United States of America #Contributed equally. (literal)
Titolo
  • A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation. (literal)
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. (literal)
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