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dc.contributor.authorNalls, Michael A.
dc.contributor.authorCouper, David J.
dc.contributor.authorTanaka, Toshiko
dc.contributor.authorvan Rooij, Frank J. A.
dc.contributor.authorChen, Ming-Huei
dc.contributor.authorSmith, Albert V.
dc.contributor.authorToniolo, Daniela
dc.contributor.authorZakai, Neil A.
dc.contributor.authorYang, Qiong
dc.contributor.authorGreinacher, Andreas
dc.contributor.authorWood, Andrew R.
dc.contributor.authorGarcia, Melissa
dc.contributor.authorGasparini, Paolo
dc.contributor.authorLiu, Yongmei
dc.contributor.authorLumley, Thomas
dc.contributor.authorFolsom, Aaron R.
dc.contributor.authorReiner, Alex P.
dc.contributor.authorGieger, Christian
dc.contributor.authorLagou, Vasiliki
dc.contributor.authorFelix, Janine F.
dc.contributor.authorVölzke, Henry
dc.contributor.authorGouskova, Natalia A.
dc.contributor.authorBiffi, Alessandro
dc.contributor.authorDöring, Angela
dc.contributor.authorVölker, Uwe
dc.contributor.authorChong, Sean
dc.contributor.authorWiggins, Kerri L.
dc.contributor.authorRendon, Augusto
dc.contributor.authorDehghan, Abbas
dc.contributor.authorMoore, Matt
dc.contributor.authorTaylor, Kent
dc.contributor.authorWilson, James G.
dc.contributor.authorLettre, Guillaume
dc.contributor.authorHofman, Albert
dc.contributor.authorBis, Joshua C.
dc.contributor.authorPirastu, Nicola
dc.contributor.authorFox, Caroline S.
dc.contributor.authorMeisinger, Christa
dc.contributor.authorSambrook, Jennifer
dc.contributor.authorArepalli, Sampath
dc.contributor.authorNauck, Matthias
dc.contributor.authorProkisch, Holger
dc.contributor.authorStephens, Jonathan
dc.contributor.authorGlazer, Nicole L.
dc.contributor.authorCupples, L. Adrienne
dc.contributor.authorOkada, Yukinori
dc.contributor.authorTakahashi, Atsushi
dc.contributor.authorKamatani, Yoichiro
dc.contributor.authorMatsuda, Koichi
dc.contributor.authorTsunoda, Tatsuhiko
dc.contributor.authorTanaka, Toshihiro
dc.contributor.authorKubo, Michiaki
dc.contributor.authorNakamura, Yusuke
dc.contributor.authorYamamoto, Kazuhiko
dc.contributor.authorKamatani, Naoyuki
dc.contributor.authorStumvoll, Michael
dc.contributor.authorTönjes, Anke
dc.contributor.authorProkopenko, Inga
dc.contributor.authorIllig, Thomas
dc.contributor.authorPatel, Kushang V.
dc.contributor.authorGarner, Stephen F.
dc.contributor.authorKuhnel, Brigitte
dc.contributor.authorMangino, Massimo
dc.contributor.authorOostra, Ben A.
dc.contributor.authorThein, Swee Lay
dc.contributor.authorCoresh, Josef
dc.contributor.authorWichmann, H.-Erich
dc.contributor.authorMenzel, Stephan
dc.contributor.authorLin, JingPing
dc.contributor.authorPistis, Giorgio
dc.contributor.authorUitterlinden, André G.
dc.contributor.authorSpector, Tim D.
dc.contributor.authorTeumer, Alexander
dc.contributor.authorEiriksdottir, Gudny
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorBandinelli, Stefania
dc.contributor.authorFrayling, Timothy M.
dc.contributor.authorChakravarti, Aravinda
dc.contributor.authorvan Duijn, Cornelia M.
dc.contributor.authorMelzer, David
dc.contributor.authorOuwehand, Willem H.
dc.contributor.authorLevy, Daniel
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorSingleton, Andrew B.
dc.contributor.authorHernandez, Dena G.
dc.contributor.authorLongo, Dan L.
dc.contributor.authorSoranzo, Nicole
dc.contributor.authorWitteman, Jacqueline C. M.
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorHarris, Tamara B.
dc.contributor.authorO'Donnell, Christopher J.
dc.contributor.authorGanesh, Santhi K.
dc.contributor.authorVisscher, Peter M.
dc.date.accessioned2019-09-30T11:56:23Z
dc.date.issued2011
dc.identifier.citationNalls, Michael A., David J. Couper, Toshiko Tanaka, Frank J. A. van Rooij, Ming-Huei Chen, Albert V. Smith, Daniela Toniolo, et al. 2011. “Multiple Loci Are Associated with White Blood Cell Phenotypes.” Edited by Peter M. Visscher. PLoS Genetics 7 (6): e1002113. https://doi.org/10.1371/journal.pgen.1002113.
dc.identifier.issn1553-7390
dc.identifier.issn1553-7404
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41426803*
dc.description.abstractWhite blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count-3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression-and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse ancestral backgrounds.
dc.language.isoen_US
dc.publisherPublic Library of Science
dash.licenseLAA
dc.titleMultiple Loci Are Associated with White Blood Cell Phenotypes
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalPLoS Genetics
dash.depositing.authorHofman, Albert::23effeffdfa95fe55437cc4d561aa487::600
dc.date.available2019-09-30T11:56:23Z
dash.workflow.comments1Science Serial ID 83966
dc.identifier.doi10.1371/journal.pgen.1002113
dash.source.volume7;6


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