Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies.
White blood cell count (WBC) is an important clinical marker that varies among different ethnic groups. African Americans are known to have a lower WBC than European Americans. We surveyed the entire genome for loci underlying this difference in WBC by using admixture mapping. We analyzed data from African American participants in the Health, Aging, and Body Composition Study and the Jackson Heart Study. Participants of both studies were genotyped across >or= 1322 single nucleotide polymorphisms that were pre-selected to be informative for African versus European ancestry and span the entire genome. We used these markers to estimate genetic ancestry in each chromosomal region and then tested the association between WBC and genetic ancestry at each locus. We found a locus on chromosome 1q strongly associated with WBC (p < 10(-12)). The strongest association was with a marker known to affect the expression of the Duffy blood group antigen. Participants who had both copies of the common West African allele had a mean WBC of 4.9 (SD 1.3); participants who had both common European alleles had a mean WBC of 7.1 (SD 1.3). This variant explained approximately 20% of population variation in WBC. We used admixture mapping, a novel method for conducting genetic-association studies, to find a region that was significantly associated with WBC on chromosome 1q. Additional studies are needed to determine the biological mechanism for this effect and its clinical implications.
Nalls
Michael A
MA
Laboratory of Epidemiology, Demography and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD 20892, USA.
Wilson
James G
JG
Patterson
Nick J
NJ
Tandon
Arti
A
Zmuda
Joseph M
JM
Huntsman
Scott
S
Garcia
Melissa
M
Hu
Donglei
D
Li
Rongling
R
Beamer
Brock A
BA
Patel
Kushang V
KV
Akylbekova
Ermeg L
EL
Files
Joe C
JC
Hardy
Cheryl L
CL
Buxbaum
Sarah G
SG
Taylor
Herman A
HA
Reich
David
D
Harris
Tamara B
TB
Ziv
Elad
E
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D002874:Chromosome Mapping / Q000379:methods*; D002878:Chromosomes, Human, Pair 1; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D044465:White People / Q000235:genetics