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Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits.
Monday,2016-08-22 10:41 America/Los_Angeles — zdrager
| Title | Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Corporate/Institutional Authors | CHARGE Consortium Hematology Working Group |
| Journal | Nat Genet |
| Volume | 48 |
| Issue | 8 |
| Pagination | 867-76 |
| Date Published | 2016 Aug |
| ISSN | 1546-1718 |
| Abstract | <p>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.</p> |
| DOI | 10.1038/ng.3607 |
| Alternate Journal | Nat. Genet. |
| PubMed ID | 27399967 |
| Grant List | R01 AG023629 / AG / NIA NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States R01 HL048801 / HL / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States R01 HL087700 / HL / NHLBI NIH HHS / United States R01 HL088215 / HL / NHLBI NIH HHS / United States R01 HL103612 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States R01 HL117078 / HL / NHLBI NIH HHS / United States R25 CA094880 / CA / NCI NIH HHS / United States RC2 HL102419 / HL / NHLBI NIH HHS / United States U01 HG005152 / HG / NHGRI NIH HHS / United States |