Sequence Variants in Three Loci Influence Monocyte Counts and Erythrocyte Volume
Open access copy at publisher website
Description
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.
Impact and interest:
Citation counts are sourced monthly from Scopus and Web of Science® citation databases.
These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.
Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.
ID Code: | 217365 | ||
---|---|---|---|
Item Type: | Contribution to Journal (Journal Article) | ||
Refereed: | Yes | ||
ORCID iD: |
|
||
Measurements or Duration: | 5 pages | ||
Keywords: | *Genome, *Monocytes, *Quantitative Trait Loci, Age Factors, Alleles, Australia, Base Sequence/*genetics, Chromosome Mapping, Chromosomes, Cohort Studies, Computer Simulation, Erythrocyte Indices/*genetics, Female, Gene Frequency | ||
DOI: | 10.1016/j.ajhg.2009.10.005 | ||
ISSN: | 1537-6605 | ||
Pure ID: | 31996348 | ||
Divisions: | Past > QUT Faculties & Divisions > Faculty of Health Past > QUT Faculties & Divisions > QUT Business School Past > QUT Faculties & Divisions > Creative Industries Faculty Current > Schools > School of Management Current > Schools > School of Biomedical Sciences Past > QUT Faculties & Divisions > Division of Research and Innovation |
||
Copyright Owner: | Consult author(s) regarding copyright matters | ||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||
Deposited On: | 06 Nov 2021 08:24 | ||
Last Modified: | 11 Jun 2024 10:28 |
Export: EndNote | Dublin Core | BibTeX
Repository Staff Only: item control page