Faculty Collaboration Database

Genome-wide association of white blood cell counts in Hispanic/Latino Americans: the Hispanic Community Health Study/Study of Latinos. Hum Mol Genet 2017 Mar 15;26(6):1193-1204

Date

02/06/2017

Pubmed ID

28158719

Pubmed Central ID

PMC5968624

DOI

10.1093/hmg/ddx024

Scopus ID

2-s2.0-85019062740 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

Circulating white blood cell (WBC) counts (neutrophils, monocytes, lymphocytes, eosinophils, basophils) differ by ethnicity. The genetic factors underlying basal WBC traits in Hispanics/Latinos are unknown. We performed a genome-wide association study of total WBC and differential counts in a large, ethnically diverse US population sample of Hispanics/Latinos ascertained by the Hispanic Community Health Study and Study of Latinos (HCHS/SOL). We demonstrate that several previously known WBC-associated genetic loci (e.g. the African Duffy antigen receptor for chemokines null variant for neutrophil count) are generalizable to WBC traits in Hispanics/Latinos. We identified and replicated common and rare germ-line variants at FLT3 (a gene often somatically mutated in leukemia) associated with monocyte count. The common FLT3 variant rs76428106 has a large allele frequency differential between African and non-African populations. We also identified several novel genetic loci involving or regulating hematopoietic transcription factors (CEBPE-SLC7A7, CEBPA and CRBN-TRNT1) associated with basophil count. The minor allele of the CEBPE variant associated with lower basophil count has been previously associated with Amerindian ancestry and higher risk of acute lymphoblastic leukemia in Hispanics. Together, these data suggest that germline genetic variation affecting transcriptional and signaling pathways that underlie WBC development and lineage specification can contribute to inter-individual as well as ethnic differences in peripheral blood cell counts (normal hematopoiesis) in addition to susceptibility to leukemia (malignant hematopoiesis).

Author List

Jain D, Hodonsky CJ, Schick UM, Morrison JV, Minnerath S, Brown L, Schurmann C, Liu Y, Auer PL, Laurie CA, Taylor KD, Browning BL, Papanicolaou G, Browning SR, Loos RJF, North KE, Thyagarajan B, Laurie CC, Thornton TA, Sofer T, Reiner AP

Author

Paul L. Auer PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Basophils
CCAAT-Enhancer-Binding Proteins
Female
Gene Frequency
Genome-Wide Association Study
Humans
Leukocyte Count
Lymphocytes
Male
Monocytes
Neutrophils
United States
fms-Like Tyrosine Kinase 3