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https://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. |
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 |
Published version: | http://dx.doi.org/10.1016/j.ajhg.2009.10.005 |
Appears in Collections: | Aurora harvest 7 Translational Health Science publications |
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