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

TitleReduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene.
Publication TypeJournal Article
Year of Publication2009
AuthorsReich D, Nalls MA, Kao LWH, Akylbekova EL, Tandon A, Patterson N, Mullikin J, Hsueh W-C, Cheng C-Y, 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
JournalPLoS Genet
Volume5
Issue1
Paginatione1000360
Date Published2009 Jan
ISSN1553-7404
KeywordsAdult, African Continental Ancestry Group, Aged, Aged, 80 and over, Case-Control Studies, Chromosomes, Human, Pair 1, Cohort Studies, Duffy Blood-Group System, European Continental Ancestry Group, Female, Genotype, Humans, Leukocyte Count, Male, Middle Aged, Neutrophils, Phenotype, Polymorphism, Single Nucleotide, Receptors, Cell Surface
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.

DOI10.1371/journal.pgen.1000360
Alternate JournalPLoS Genet
PubMed ID19180233
PubMed Central IDPMC2628742
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
K01 DK067207 / DK / NIDDK NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
U01 HG004168 / HG / NHGRI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
R01-HL-084107 / HL / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
K01DK067207 / DK / NIDDK NIH HHS / United States
R21 DK073482 / DK / NIDDK NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01HC95171 / HL / NHLBI NIH HHS / United States
N01-HC-95170 / HC / NHLBI NIH HHS / United States
N01HC95172 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R21DK073482 / DK / NIDDK NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01HC95170 / HL / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
R01 HL084107 / HL / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01-HC-95171 / HC / NHLBI NIH HHS / United States
/ ImNIH / Intramural NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01-HC-95172 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
U54 RR020278 / RR / NCRR NIH HHS / United States
U01-HG004168 / HG / NHGRI NIH HHS / United States