Abstract
Platelet count is a highly heritable trait with genetic factors responsible for around 80% of the phenotypic variance. We measured platelet count longitudinally in 327 monozygotic and 418 dizygotic twin pairs at 12, 14 and 16 years of age. We also performed a genome-wide linkage scan of these twins and their families in an attempt to localize QTLs that influenced variation in platelet concentrations. Suggestive linkage was observed on chromosome 19q13.13–19q13.31 at 12 (LOD=2.12, P=0.0009), 14 (LOD=2.23, P=0.0007) and 16 (LOD=1.01, P=0.016) years of age and multivariate analysis of counts at all three ages increased the LOD to 2.59 (P=0.0003). A possible candidate in this region is the gene for glycoprotein VI, a receptor involved in platelet aggregation. Smaller linkage peaks were also seen at 2p, 5p, 5q, 10p and 15q. There was little evidence for linkage to the chromosomal regions containing the genes for thrombopoietin (3q27) and the thrombopoietin receptor (1q34), suggesting that polymorphisms in these genes do not contribute substantially to variation in platelet count between healthy individuals.
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Acknowledgements
Collection of phenotypes and DNA samples was supported by grants from the Queensland Cancer Fund, the Australian National Health and Medical Research Council (950998, 981339 and 241944) and the US National Cancer Institute (CA88363) to Dr Nick Hayward. The genome scans were supported by the Australian NHMRC's Program in Medical Genomics and funding from the Center for Inherited Disease Research (Director, Dr Jerry Roberts) at Johns Hopkins University to Dr Jeff Trent. We thank Ann Eldridge, Marlene Grace and Anjali Henders for assistance and the twins, their siblings, and their parents for their cooperation.
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Evans, D., Zhu, G., Duffy, D. et al. Multivariate QTL linkage analysis suggests a QTL for platelet count on chromosome 19q. Eur J Hum Genet 12, 835–842 (2004). https://doi.org/10.1038/sj.ejhg.5201248
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DOI: https://doi.org/10.1038/sj.ejhg.5201248
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