Sequence variants in three loci influence monocyte counts and erythrocyte volume

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dc.contributor.authorFerreira, M.
dc.contributor.authorHottenga, J.
dc.contributor.authorWarrington, N.
dc.contributor.authorMedland, S.
dc.contributor.authorWillemsen, G.
dc.contributor.authorLawrence, R.
dc.contributor.authorGordon, S.
dc.contributor.authorde Geus, E.
dc.contributor.authorHenders, A.
dc.contributor.authorSmit, J.
dc.contributor.authorCampbell, M.
dc.contributor.authorWallace, L.
dc.contributor.authorEvans, D.
dc.contributor.authorWright, M.
dc.contributor.authorNyholt, D.
dc.contributor.authorJames, A.
dc.contributor.authorBeilby, J.
dc.contributor.authorPenninx, B.
dc.contributor.authorPalmer, L.
dc.contributor.authorFrazer, I.
dc.contributor.authoret al.
dc.date.issued2009
dc.description.abstractBlood 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.
dc.description.statementofresponsibilityManuel A.R. Ferreira ... Lyle J. Palmer ... et al.
dc.identifier.citationAmerican Journal of Human Genetics, 2009; 85(5):745-749
dc.identifier.doi10.1016/j.ajhg.2009.10.005
dc.identifier.issn0002-9297
dc.identifier.issn1537-6605
dc.identifier.orcidPalmer, L. [0000-0002-1628-3055]
dc.identifier.urihttp://hdl.handle.net/2440/88484
dc.language.isoen
dc.publisherElsevier
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/241944
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/339462
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/389927
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/389875
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/389891
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/389892
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/389938
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/443036
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/442915
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/442981
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/496739
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/552485
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/552498
dc.relation.granthttp://purl.org/au-research/grants/arc/DP0212016
dc.relation.granthttp://purl.org/au-research/grants/arc/DP0343921
dc.rights© 2009 by The American Society of Human Genetics. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.ajhg.2009.10.005
dc.subjectMonocytes
dc.subjectChromosomes, Human, Pair 6
dc.subjectChromosomes, Human, Pair 9
dc.subjectHumans
dc.subjectLeukocyte Count
dc.subjectPlatelet Count
dc.subjectErythrocyte Indices
dc.subjectCohort Studies
dc.subjectChromosome Mapping
dc.subjectGenetics, Population
dc.subjectAge Factors
dc.subjectBase Sequence
dc.subjectGene Frequency
dc.subjectGenotype
dc.subjectHaplotypes
dc.subjectLinkage Disequilibrium
dc.subjectPhenotype
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAlleles
dc.subjectQuantitative Trait Loci
dc.subjectGenome, Human
dc.subjectComputer Simulation
dc.subjectAustralia
dc.subjectNetherlands
dc.subjectFemale
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.titleSequence variants in three loci influence monocyte counts and erythrocyte volume
dc.typeJournal article
pubs.publication-statusPublished

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