Reduced Neutrophil Count in People of african Descent Is Due to a Regulatory Variant in the Duffy antigen Receptor For Chemokines Gene

Authors

David Reich, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America
Michael A. Nalls, Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, United States of America; Laboratory of Epidemiology, Demography and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, United States of America
W H Linda Kao
Ermeg L. Akylbekova
Arti Tandon
Nick Patterson
James Mullikin
Wen-Chi Hsueh
Ching-Yu Cheng
Josef Coresh
Eric Boerwinkle, Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, United States of AmericaFollow
Man Li
Alicja Waliszewska
Julie Neubauer
Rongling Li
Tennille S. Leak
Lynette Ekunwe
Joe C. Files
Cheryl L. Hardy
Joseph M. Zmuda
Herman A. Taylor
Elad Ziv
Tamara B. Harris
James G. Wilson

Publication Date

1-1-2009

Journal

PLOS Genetics

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.

Keywords

Adult, 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

Comments

PMCID: PMC2628742

Article in PLoS