title: Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene.
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.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America. reich@genetics.med.harvard.edu
authors.forename: David
authors.initials: D
authors.lastname: Reich
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalls
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
authors.forename: Ermeg L
authors.initials: EL
authors.lastname: Akylbekova
authors.forename: Arti
authors.initials: A
authors.lastname: Tandon
authors.forename: Nick
authors.initials: N
authors.lastname: Patterson
authors.forename: James
authors.initials: J
authors.lastname: Mullikin
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Hsueh
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Alicja
authors.initials: A
authors.lastname: Waliszewska
authors.forename: Julie
authors.initials: J
authors.lastname: Neubauer
authors.forename: Rongling
authors.initials: R
authors.lastname: Li
authors.forename: Tennille S
authors.initials: TS
authors.lastname: Leak
authors.forename: Lynette
authors.initials: L
authors.lastname: Ekunwe
authors.forename: Joe C
authors.initials: JC
authors.lastname: Files
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Hardy
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Zmuda
authors.forename: Herman A
authors.initials: HA
authors.lastname: Taylor
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D015331:Cohort Studies; D004375:Duffy Blood-Group System / Q000235:genetics* / Q000276:immunology; D005260:Female; D005838:Genotype; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry* / Q000276:immunology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000276:immunology; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: C473745:ACKR1 protein, human; D004375:Duffy Blood-Group System; D011956:Receptors, Cell Surface