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

Deepti Jain, Chani J. Hodonsky, Ursula M. Schick, Jean V. Morrison, Sharon Minnerath, Lisa Brown, Claudia Schurmann, Yongmei Liu, Paul L. Auer, Cecelia A. Laurie, Kent D. Taylor, Brian L. Browning, George Papanicolaou, Sharon R. Browning, Ruth J.F. Loos, Kari E. North, Bharat Thyagarajan, Cathy C. Laurie, Timothy A. Thornton, Tamar SoferAlexander P. Reiner

Research output: Contribution to journalArticlepeer-review

23 Scopus 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).

Original languageEnglish (US)
Article numberddx024
Pages (from-to)1193-1204
Number of pages12
JournalHuman molecular genetics
Volume26
Issue number6
DOIs
StatePublished - Mar 15 2017

Bibliographical note

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© The Author 2017. Published by Oxford University Press. All rights reserved.

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