Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits

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Author
Pankratz, Nathan
Schick, Ursula M
Zhou, Yi
Zhou, Wei
Ahluwalia, Tarunveer Singh
Allende, Maria Laura
Auer, Paul L
Bork-Jensen, Jette
Brody, Jennifer A
Chen, Ming-Huei
Clavo, Vinna
Eicher, John D
Grarup, Niels
Hu, Bella
Hunker, Kristina
Johnson, Andrew D
Leusink, Maarten
Lu, Yingchang
Lyytikäinen, Leo-Pekka
Manichaikul, Ani
Marioni, Riccardo E
Nalls, Mike A
Pazoki, Raha
Smith, Albert Vernon
van Rooij, Frank J A
Yang, Min-Lee
Zhang, Xiaoling
Zhang, Yan
Asselbergs, Folkert W
Boerwinkle, Eric
Borecki, Ingrid B
Bottinger, Erwin P
Cushman, Mary
de Bakker, Paul I W
Deary, Ian J
Dong, Liguang
Feitosa, Mary F
Floyd, James S
Franceschini, Nora
Franco, Oscar H
Garcia, Melissa E
Grove, Megan L
Gudnason, Vilmundur
Hansen, Torben
Harris, Tamara B
Jackson, Rebecca D
Jia, Jia
Kähönen, Mika
Launer, Lenore J
Lehtimäki, Terho
Liewald, David C
Linneberg, Allan
Liu, Yongmei
Loos, Ruth J F
Numans, Mattijs E
Pedersen, Oluf
Psaty, Bruce M
Raitakari, Olli T
Rich, Stephen S
Rivadeneira, Fernando
Di Sant, Amanda M Rosa
Rotter, Jerome I
Starr, John M
Taylor, Kent D
Thuesen, Betina Heinsbæk
Tracy, Russell P
Uitterlinden, Andre G
Wang, Jiansong
Wang, Judy
Dehghan, Abbas
Huo, Yong
Cupples, L Adrienne
Wilson, James G
Proia, Richard L
O’Donnell, Christopher J
Reiner, Alex P
Ganesh, Santhi K
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ng.3607Metadata
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Pankratz, 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.Abstract
Hematologic 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5145000/pdf/Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:30371136
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