Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/88484
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Type: Journal article
Title: Sequence variants in three loci influence monocyte counts and erythrocyte volume
Author: Ferreira, M.
Hottenga, J.
Warrington, N.
Medland, S.
Willemsen, G.
Lawrence, R.
Gordon, S.
de Geus, E.
Henders, A.
Smit, J.
Campbell, M.
Wallace, L.
Evans, D.
Wright, M.
Nyholt, D.
James, A.
Beilby, J.
Penninx, B.
Palmer, L.
Frazer, I.
et al.
Citation: American Journal of Human Genetics, 2009; 85(5):745-749
Publisher: Elsevier
Issue Date: 2009
ISSN: 0002-9297
1537-6605
Statement of
Responsibility: 
Manuel A.R. Ferreira ... Lyle J. Palmer ... et al.
Abstract: Blood cells participate in vital physiological processes, and their numbers are tightly regulated so that homeostasis is maintained. Disruption of key regulatory mechanisms underlies many blood-related Mendelian diseases but also contributes to more common disorders, including atherosclerosis. We searched for quantitative trait loci (QTL) for hematology traits through a whole-genome association study, because these could provide new insights into both hemopoeitic and disease mechanisms. We tested 1.8 million variants for association with 13 hematology traits measured in 6015 individuals from the Australian and Dutch populations. These traits included hemoglobin composition, platelet counts, and red blood cell and white blood cell indices. We identified three regions of strong association that, to our knowledge, have not been previously reported in the literature. The first was located in an intergenic region of chromosome 9q31 near LPAR1, explaining 1.5% of the variation in monocyte counts (best SNP rs7023923, p = 8.9 × 10−14). The second locus was located on chromosome 6p21 and associated with mean cell erythrocyte volume (rs12661667, p = 1.2 × 10−9, 0.7% variance explained) in a region that spanned five genes, including CCND3, a member of the D-cyclin gene family that is involved in hematopoietic stem cell expansion. The third region was also associated with erythrocyte volume and was located in an intergenic region on chromosome 6q24 (rs592423, p = 5.3 × 10−9, 0.6% variance explained). All three loci replicated in an independent panel of 1543 individuals (p values = 0.001, 9.9 × 10−5, and 7 × 10−5, respectively). The identification of these QTL provides new opportunities for furthering our understanding of the mechanisms regulating hemopoietic cell fate.
Keywords: Monocytes; Chromosomes, Human, Pair 6; Chromosomes, Human, Pair 9; Humans; Leukocyte Count; Platelet Count; Erythrocyte Indices; Cohort Studies; Chromosome Mapping; Genetics, Population; Age Factors; Base Sequence; Gene Frequency; Genotype; Haplotypes; Linkage Disequilibrium; Phenotype; Polymorphism, Single Nucleotide; Alleles; Quantitative Trait Loci; Genome, Human; Computer Simulation; Australia; Netherlands; Female; Male; Genome-Wide Association Study
Rights: © 2009 by The American Society of Human Genetics. All rights reserved.
RMID: 0020136646
DOI: 10.1016/j.ajhg.2009.10.005
Grant ID: http://purl.org/au-research/grants/nhmrc/241944
http://purl.org/au-research/grants/nhmrc/339462
http://purl.org/au-research/grants/nhmrc/389927
http://purl.org/au-research/grants/nhmrc/389875
http://purl.org/au-research/grants/nhmrc/389891
http://purl.org/au-research/grants/nhmrc/389892
http://purl.org/au-research/grants/nhmrc/389938
http://purl.org/au-research/grants/nhmrc/443036
http://purl.org/au-research/grants/nhmrc/442915
http://purl.org/au-research/grants/nhmrc/442981
http://purl.org/au-research/grants/nhmrc/496739
http://purl.org/au-research/grants/nhmrc/552485
http://purl.org/au-research/grants/nhmrc/552498
http://purl.org/au-research/grants/arc/DP0212016
http://purl.org/au-research/grants/arc/DP0343921
Appears in Collections:Translational Health Science publications

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