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

Publication ,  Journal Article
CHARGE Consortium Hematology Working Group,
Published in: Nat Genet
August 2016

Hematologic measures such as hematocrit and white blood cell (WBC) count are heritable and clinically relevant. We analyzed erythrocyte and WBC phenotypes in 52,531 individuals (37,775 of European ancestry, 11,589 African Americans, and 3,167 Hispanic Americans) from 16 population-based cohorts with Illumina HumanExome BeadChip genotypes. We then performed replication analyses of new discoveries in 18,018 European-American women and 5,261 Han Chinese. We identified and replicated four new erythrocyte trait-locus associations (CEP89, SHROOM3, FADS2, and APOE) and six new WBC loci for neutrophil count (S1PR4), monocyte count (BTBD8, NLRP12, and IL17RA), eosinophil count (IRF1), and total WBC count (MYB). The 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 for S1pr4 in mouse and s1pr4 in zebrafish demonstrated phenotypes consistent with the association observed in humans and altered kinetics of neutrophil recruitment and resolution in response to tissue injury.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

August 2016

Volume

48

Issue

8

Start / End Page

867 / 876

Location

United States

Related Subject Headings

  • Zebrafish
  • Receptors, Lysosphingolipid
  • Quantitative Trait Loci
  • Mice
  • Male
  • Humans
  • Hematocrit
  • Genome-Wide Association Study
  • Genetic Loci
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
CHARGE Consortium Hematology Working Group, . (2016). Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits. Nat Genet, 48(8), 867–876. https://doi.org/10.1038/ng.3607
CHARGE Consortium Hematology Working Group, S. K. “Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits.Nat Genet 48, no. 8 (August 2016): 867–76. https://doi.org/10.1038/ng.3607.
CHARGE Consortium Hematology Working Group. Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits. Nat Genet. 2016 Aug;48(8):867–76.
CHARGE Consortium Hematology Working Group, S. K. “Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits.Nat Genet, vol. 48, no. 8, Aug. 2016, pp. 867–76. Pubmed, doi:10.1038/ng.3607.
CHARGE Consortium Hematology Working Group. Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits. Nat Genet. 2016 Aug;48(8):867–876.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

August 2016

Volume

48

Issue

8

Start / End Page

867 / 876

Location

United States

Related Subject Headings

  • Zebrafish
  • Receptors, Lysosphingolipid
  • Quantitative Trait Loci
  • Mice
  • Male
  • Humans
  • Hematocrit
  • Genome-Wide Association Study
  • Genetic Loci
  • Female