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

Soranzo, N; Rendon, A; Gieger, C; Jones, CI; Watkins, NA; Menzel, S; Döring, A; Stephens, J; Prokisch, H; Erber, W; Potter, SC; Bray, SL; Burns, P; Jolley, J; Falchi, M; Kühnel, B; Erdmann, J; Schunkert, H; Samani, NJ; Illig, T; Garner, SF; Rankin, A; Meisinger, C; Bradley, JR; Thein, SL; Goodall, AH; Spector, TD; Deloukas, P; Ouwehand, WH

doi:10.1182/blood-2008-10-184234

journal article

Title:: A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function.
Document type:: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't; Twin Study
Author(s):: Soranzo, N; Rendon, A; Gieger, C; Jones, CI; Watkins, NA; Menzel, S; Döring, A; Stephens, J; Prokisch, H; Erber, W; Potter, SC; Bray, SL; Burns, P; Jolley, J; Falchi, M; Kühnel, B; Erdmann, J; Schunkert, H; Samani, NJ; Illig, T; Garner, SF; Rankin, A; Meisinger, C; Bradley, JR; Thein, SL; Goodall, AH; Spector, TD; Deloukas, P; Ouwehand, WH
Abstract:: 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.
Journal title abbreviation:: Blood
Year:: 2009
Journal volume:: 113
Journal issue:: 16
Pages contribution:: 3831-7
Language:: eng
Fulltext / DOI:: doi:10.1182/blood-2008-10-184234
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/19221038
Print-ISSN:: 0006-4971
TUM Institution:: Institut für Humangenetik
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Institut für Humangenetik (Prof. Winkelmann)2009

mediaTUM Gesamtbestand Hochschulbibliographie 2009 Fakultäten Medizin Institut für Humangenetik