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Genome-wide association of white blood cell counts in Hispanic/Latino Americans: the Hispanic Community Health Study/Study of Latinos.

TitleGenome-wide association of white blood cell counts in Hispanic/Latino Americans: the Hispanic Community Health Study/Study of Latinos.
Publication TypePublication
Year2017
AuthorsJain 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
JournalHum Mol Genet
Volume26
Issue6
Pagination1193-1204
Date Published2017 03 15
ISSN1460-2083
KeywordsAfrican Americans, Basophils, CCAAT-Enhancer-Binding Proteins, European Continental Ancestry Group, Female, fms-Like Tyrosine Kinase 3, Gene Frequency, genome-wide association study, Hispanic Americans, Humans, Leukocyte Count, Lymphocytes, Male, Monocytes, Neutrophils, United States
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).

DOI10.1093/hmg/ddx024
Alternate JournalHum Mol Genet
PubMed ID28158719
PubMed Central IDPMC5968624
Grant ListU01 HG007417 / HG / NHGRI NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
K08 DK093705 / DK / NIDDK NIH HHS / United States
P01 GM099568 / GM / NIGMS NIH HHS / United States
R01 HL129132 / HL / NHLBI NIH HHS / United States
R01 GM110068 / GM / NIGMS NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
R01 DK101855 / DK / NIDDK NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
U54 TR000123 / TR / NCATS NIH HHS / United States
T32 GM081062 / GM / NIGMS NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
MS#: 
0298
Manuscript Lead/Corresponding Author Affiliation: 
HCHS/SOL Genetic Analysis Center - University of Washington, Seattle
ECI: 
Manuscript Status: 
Published