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Soranzo, N.* ; Rendon, A.* ; Gieger, C. ; Jones, C.I.* ; Watkins, N.A.* ; Menzel, S.* ; Döring, A. ; Stephens, J.* ; Prokisch, H. ; Erber, W.* ; Potter, S.C.* ; Bray, S.L.* ; Burns, P.* ; Jolley, J.* ; Falchi, M.* ; Kühnel, B. ; Erdmann, J.* ; Schunkert, H.* ; Samani, N.J.* ; Illig, T. ; Garner, S.F.* ; Rankin, A.* ; Meisinger, C. ; Bradley, J.R.* ; Thein, S.L.* ; Goodall, A.H.* ; Spector, T.D.* ; Deloukas, P.* ; Ouwehand, W.H.

A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function.

Blood 113, 3831-3837 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits. We performed a genome-wide association study for MPV and identified one SNP, rs342293, as having highly significant and reproducible association with MPV (per-G allele effect 0.016 +/- 0.001 log fL; P < 1.08 x 10(-24)) and PLT (per-G effect -4.55 +/- 0.80 10(9)/L; P < 7.19 x 10(-8)) in 8586 healthy subjects. Whole-genome expression analysis in the 1-MB region showed a significant association with platelet transcript levels for PIK3CG (n = 35; P = .047). The G allele at rs342293 was also associated with decreased binding of annexin V to platelets activated with collagen-related peptide (n = 84; P = .003). The region 7q22.3 identifies the first QTL influencing platelet volume, counts, and function in healthy subjects. Notably, the association signal maps to a chromosome region implicated in myeloid malignancies, indicating this site as an important regulatory site for hematopoiesis. The identification of loci regulating MPV by this and other studies will increase our insight in the processes of megakaryopoiesis and proplatelet formation, and it may aid the identification of genes that are somatically mutated in essential thrombocytosis.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords genome-wide association; dependent protein-kinase; blood cell counts; proplatelet formation; transcription factor; differentiated megakaryocytes; gene; microarray; disorders; loci
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 113, Issue: 16, Pages: 3831-3837 Article Number: , Supplement: ,
Publisher American Society of Hematology
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)