Academic Journal
A Genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation
| العنوان: | 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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| المؤلفون: | Uzzau, Sergio, Cucca, Francesco, Naitza, Silvia, Porcu, Elenora, Steri, Maristella, Mulas, Antonella, Xiao, Xiang, Strait, James, Dei, Mariano, Busonero, Fabio, Maschio, Andrea, Zoledziewska, Magdalena, Sidore, Carlo, Pitzalis, Maristella, Loi, Alessia, Piras, Roberta, Crisponi, Laura, Concas, Antonio, Podda, Carlo, Longo, Dan L., Lakatta, Edward G., Cao, Antonio, Schlessinger, David, Uda, Manuela, Sanna, Serena, Taub, Dennis Daniel, Lai, Sandra, Usala, Gianluca, Zara, Ilenia, Virdis, Francesca, Whalen, Michael B., Scheet, Paul, Abecasis, Gonçalo, Deidda, Francesca |
| المساهمون: | Uzzau, Sergio, Cucca, Francesco, Naitza, Silvia, Porcu, Elenora, Steri, Maristella, Mulas, Antonella, Xiao, Xiang, Strait, Jame, Dei, Mariano, Busonero, Fabio, Maschio, Andrea, Zoledziewska, Magdalena, Sidore, Carlo, Pitzalis, Maristella, Loi, Alessia, Piras, Roberta, Crisponi, Laura, Concas, Antonio, Podda, Carlo, Longo, Dan L., Lakatta, Edward G., Cao, Antonio, Schlessinger, David, Uda, Manuela, Sanna, Serena, Taub, Dennis Daniel, Lai, Sandra, Usala, Gianluca, Zara, Ilenia, Virdis, Francesca, Whalen, Michael B., Scheet, Paul, Abecasis, Gonçalo, Deidda, Francesca |
| بيانات النشر: | Public Library of Science |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Genome-wide association scan (GWAS), pro-inflammatory molecule, erythrocyte sedimentation rate (ESR) |
| الوصف: | 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) andUCN119B/SPPL3(rs11829037, p = 8.91×10−10) loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53×10−13) and inCADM3(rs3026968, p = 7.63×10−13); for hsCRP, within theCRPgene (rs3093077, p = 5.73×10−21), nearDARC(rs3845624, p = 1.43×10−10),UNC119B/SPPL3(rs11829037, p = 1.50×10−14), andICOSLG/AIRE(rs113459440, p = 1.54×10−08) loci. Confirmatory evidence was found for IL-6 in theIL-6Rgene (rs4129267); for ESR atCR1(rs12567990) andTMEM57(rs10903129); for MCP-1 at DARC (rs12075); and for hsCRP at CRP (rs1205),HNF1A(rs225918), andAPOC-I(rs4420638). Our results improve the current knowledge of genetic variants underlying inflammation and provide novel clues for the understanding ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/WOS:000300223400039; volume:8; issue:1; journal:PLOS GENETICS; http://hdl.handle.net/11388/261536 |
| DOI: | 10.1371/journal.pgen.1002480 |
| الاتاحة: | http://hdl.handle.net/11388/261536 https://doi.org/10.1371/journal.pgen.1002480 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E4777388 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pgen.1002480 |
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