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PMID: 19221038 Published · ppublish English Journal Article Multicenter Study Research Support, Non-U.S. Gov't Twin Study

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

Blood ·Vol. 113 ·No. 16 ·2009-04-16 ·Pages 3831-7

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.

MeSH Terms
Adult Aged Blood Platelets Chromosome Mapping Chromosomes, Human, Pair 7/genetics Cohort Studies Female Gene Expression Regulation/genetics Genome, Human/genetics Hematologic Neoplasms/genetics Humans Male Middle Aged Platelet Count Polymorphism, Single Nucleotide Quantitative Trait Loci/genetics Thrombocythemia, Essential/genetics Thrombopoiesis/genetics
Authors & Affiliations
29 authors, click to expand affiliations / ORCID
Soranzo Nicole
Human Genetics Department, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom. ns6@sanger.ac.uk
Rendon Augusto
Gieger Christian
Jones Chris I
Watkins Nicholas A
Menzel Stephan
Döring Angela
Stephens Jonathan
Prokisch Holger
Erber Wendy
Potter Simon C
Bray Sarah L
Burns Philippa
Jolley Jennifer
Falchi Mario
Kühnel Brigitte
Erdmann Jeanette
Schunkert Heribert
Samani Nilesh J
Illig Thomas
Garner Stephen F
Rankin Angela
Meisinger Christa
Bradley John R
Thein Swee Lay
Goodall Alison H
Spector Tim D
Deloukas Panos
Ouwehand Willem H
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
1528-0020
DOI
10.1182/blood-2008-10-184234
Email
ns6@sanger.ac.uk
Published
2009-04-16
Epub
2009-00-12
Pages
3831-7
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC2714088
Subset
IM
Grants
Wellcome Trust · 072856 · United Kingdom
Medical Research Council · G0000111 · United Kingdom
Wellcome Trust · 077011 · United Kingdom
Wellcome Trust · 079771 · United Kingdom
Wellcome Trust · United Kingdom
Wellcome Trust · 084183 · United Kingdom
Wellcome Trust · 082597 · United Kingdom
External Links
PubMed source DOI: 10.1182/blood-2008-10-184234 PMC Full Text View journal details
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