Title | Genome-wide association of white blood cell counts in Hispanic/Latino Americans: the Hispanic Community Health Study/Study of Latinos. |
Publication Type | Publication |
Year | 2017 |
Authors | 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 |
Journal | Hum Mol Genet |
Volume | 26 |
Issue | 6 |
Pagination | 1193-1204 |
Date Published | 2017 Mar 15 |
ISSN | 1460-2083 |
Keywords | Basophils, Black or African American, CCAAT-Enhancer-Binding Proteins, Female, fms-Like Tyrosine Kinase 3, Gene Frequency, genome-wide association study, Hispanic or Latino, Humans, Leukocyte Count, Lymphocytes, Male, Monocytes, Neutrophils, United States, White People |
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). |
DOI | 10.1093/hmg/ddx024 |
Alternate Journal | Hum Mol Genet |
PubMed ID | 28158719 |
PubMed Central ID | PMC5968624 |
Grant List | U01 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 |
Genome-wide association of white blood cell counts in Hispanic/Latino Americans: the Hispanic Community Health Study/Study of Latinos.
MS#:
0298
ECI:
Yes
Manuscript Status:
Published