Pankratz, NathanSchick, Ursula MZhou, YiZhou, WeiAhluwalia, Tarunveer SinghAllende, Maria LauraAuer, Paul LBork-Jensen, JetteBrody, Jennifer AChen, Ming-HueiClavo, VinnaEicher, John DGrarup, NielsHagedorn, ElliottHu, BellaHunker, KristinaJohnson, Andrew DLeusink, MaartenLu, YingchangLyytikäinen, Leo-PekkaManichaikul, AniMarioni, Riccardo ENalls, Mike APazoki, RahaSmith, Albert Vernonvan Rooij, Frank J AYang, Min-LeeZhang, XiaolingZhang, YanAsselbergs, Folkert WBoerwinkle, EricBorecki, Ingrid BBottinger, Erwin PCushman, Maryde Bakker, Paul I WDeary, Ian JDong, LiguangFeitosa, Mary FFloyd, James SFranceschini, NoraFranco, Oscar HGarcia, Melissa EGrove, Megan LGudnason, VilmundurHansen, TorbenHarris, Tamara BHofman, AlbertJackson, Rebecca DJia, JiaKähönen, MikaLauner, Lenore JLehtimäki, TerhoLiewald, David CLinneberg, AllanLiu, YongmeiLoos, Ruth J FNguyen, VyNumans, Mattijs EPedersen, OlufPsaty, Bruce MRaitakari, Olli TRich, Stephen SRivadeneira, FernandoDi Sant, Amanda M RosaRotter, Jerome IStarr, John MTaylor, Kent DThuesen, Betina HeinsbækTracy, Russell PUitterlinden, Andre GWang, JiansongWang, JudyDehghan, AbbasHuo, YongCupples, L AdrienneWilson, James GProia, Richard LZon, LeonardO’Donnell, Christopher JReiner, Alex PGanesh, Santhi K2017-02-182016Pankratz, N., U. M. Schick, Y. Zhou, W. Zhou, T. S. Ahluwalia, M. L. Allende, P. L. Auer, et al. 2016. “Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits.” Nature genetics 48 (8): 867-876. doi:10.1038/ng.3607. http://dx.doi.org/10.1038/ng.3607.1061-4036http://nrs.harvard.edu/urn-3:HUL.InstRepos:30371136Hematologic measures such as hematocrit and white blood cell (WBC) count are heritable and clinically relevant. Erythrocyte and WBC phenotypes were analyzed with Illumina HumanExome BeadChip genotypes in 52,531 individuals (37,775 of European ancestry; 11,589 African Americans; 3,167 Hispanic Americans) from 16 population-based cohorts. We then performed replication analyses of novel discoveries in 18,018 European American women and 5,261 Han Chinese. We identified and replicated four novel erythrocyte trait-locus associations (CEP89, SHROOM3, FADS2, and APOE) and six novel WBC loci for neutrophil count (S1PR4), monocyte count (BTBD8, NLRP12, and IL17RA), eosinophil count (IRF1), and total WBC (MYB). The novel association of a rare missense variant in S1PR4 supports the role of sphingosine-1-phosphate signaling in leukocyte trafficking and circulating neutrophil counts. Loss-of-function experiments of S1pr4 in mouse and zebrafish demonstrated phenotypes consistent with the association observed in humans and altered kinetics of neutrophil recruitment and resolution in response to tissue injury.en-USJournal Article2017-02-1810.1038/ng.3607