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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

Reich, D and Nalls, MA and Kao, WHL and Akylbekova, EL and Tandon, A and Patterson, N and Mullikin, J and Hsueh, WC and Cheng, CY and Coresh, J and Boerwinkle, E and Li, M and Waliszewska, A and Neubauer, J and Li, R and Leak, TS and Ekunwe, L and Files, JC and Hardy, CL and Zmuda, JM and Taylor, HA and Ziv, E and Harris, TB and Wilson, JG (2009) Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. PLoS Genetics, 5 (1). ISSN 1553-7390

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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 = 3.8610-5), establishing a novel phenotype for this genetic variant.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Reich, D
Nalls, MA
Kao, WHL
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, JMZmudaJ@edc.pitt.eduEPIDJMZ
Taylor, HA
Ziv, E
Harris, TB
Wilson, JG
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorVisscher, Peter M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 January 2009
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 5
Number: 1
DOI or Unique Handle: 10.1371/journal.pgen.1000360
Schools and Programs: School of Public Health > Epidemiology
Refereed: Yes
ISSN: 1553-7390
PubMed Central ID: PMC2628742
PubMed ID: 19180233
Date Deposited: 24 Jul 2012 18:54
Last Modified: 22 Jun 2021 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/13099

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