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PMID: 19180233 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, U.S. Gov't, Non-P.H.S.

Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene.

PLoS genetics ·Vol. 5 ·No. 1 ·2009-01-00 ·Pages e1000360

Reich D, Nalls MA, Kao WH, Akylbekova EL, Tandon A, Patterson N, Mullikin J, Hsueh WC, Cheng CY, Coresh J, Boerwinkle E, Li M, Waliszewska A, Neubauer J, Li R, Leak TS, Ekunwe L, Files JC, Hardy CL, Zmuda JM, Taylor HA, Ziv E, Harris TB, Wilson JG

Abstract

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8 x 10(-5)), establishing a novel phenotype for this genetic variant.

MeSH Terms
Adult Aged Aged, 80 and over Blacks/genetics Case-Control Studies Chromosomes, Human, Pair 1/genetics Cohort Studies Duffy Blood-Group System/genetics,immunology Female Genotype Humans Leukocyte Count Male Middle Aged Neutrophils/chemistry,immunology Phenotype Polymorphism, Single Nucleotide Receptors, Cell Surface/genetics,immunology Whites/genetics
Chemicals
ACKR1 protein, human Duffy Blood-Group System Receptors, Cell Surface
Authors & Affiliations
24 authors, click to expand affiliations / ORCID
Reich David
Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America. [email protected]
Nalls Michael A
Kao W H Linda
Akylbekova Ermeg L
Tandon Arti
Patterson Nick
Mullikin James
Hsueh Wen-Chi
Cheng Ching-Yu
Coresh Josef
Boerwinkle Eric
Li Man
Waliszewska Alicja
Neubauer Julie
Li Rongling
Leak Tennille S
Ekunwe Lynette
Files Joe C
Hardy Cheryl L
Zmuda Joseph M
Taylor Herman A
Ziv Elad
Harris Tamara B
Wilson James G
Conflict of Interest

The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1000360
Email
[email protected]
Published
2009-01-00
Epub
2009-00-30
Pages
e1000360
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2628742
Subset
IM
Grants
NHLBI NIH HHS · N01HC55020 · United States
NIDDK NIH HHS · K01 DK067207 · United States
NHLBI NIH HHS · N01HC55018 · United States
NHGRI NIH HHS · U01 HG004168 · United States
NHLBI NIH HHS · N01-HC-55016 · United States
NHLBI NIH HHS · R01-HL-084107 · United States
NHLBI NIH HHS · N01HC55015 · United States
NIDDK NIH HHS · K01DK067207 · United States
NIDDK NIH HHS · R21 DK073482 · United States
NHLBI NIH HHS · N01-HC-55015 · United States
NHLBI NIH HHS · N01HC95171 · United States
NHLBI NIH HHS · N01-HC-95170 · United States
NHLBI NIH HHS · N01HC95172 · United States
NHLBI NIH HHS · N01-HC-55022 · United States
NIDDK NIH HHS · R21DK073482 · United States
NHLBI NIH HHS · N01HC55022 · United States
NHLBI NIH HHS · N01-HC-55021 · United States
NHLBI NIH HHS · N01HC95170 · United States
NHLBI NIH HHS · N01-HC-55019 · United States
NHLBI NIH HHS · R01 HL084107 · United States
NHLBI NIH HHS · N01-HC-55020 · United States
NHLBI NIH HHS · N01HC55016 · United States
NHLBI NIH HHS · N01-HC-95171 · United States
Intramural NIH HHS · United States
NHLBI NIH HHS · N01HC55019 · United States
NHLBI NIH HHS · N01-HC-95172 · United States
NHLBI NIH HHS · N01-HC-55018 · United States
NHLBI NIH HHS · N01HC55021 · United States
NCRR NIH HHS · U54 RR020278 · United States
NHGRI NIH HHS · U01-HG004168 · United States
External Links
PubMed source DOI: 10.1371/journal.pgen.1000360 PMC Full Text View journal details
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