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

Nicole Soranzo; Augusto Rendon; Christian Gieger; Chris I. Jones; Nicholas A. Watkins; Stephan Menzel; Angela Döring; Jonathan Stephens; Holger Prokisch; Wendy Erber; Simon C. Potter; Sarah L. Bray; Philippa Burns; Jennifer Jolley; Mario Falchi; Brigitte Kühnel; Jeanette Erdmann; Heribert Schunkert; Nilesh J. Samani; Thomas Illig; Stephen F. Garner; Angela Rankin; Christa Meisinger; John R. Bradley; Swee Lay Thein; Alison H. Goodall; Tim D. Spector; Panos Deloukas; Willem H. Ouwehand

doi:10.1182/blood-2008-10-184234

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

Nicole Soranzo, Augusto Rendon, Christian Gieger, Chris I. Jones, Nicholas A. Watkins, Stephan Menzel, Angela Döring, Jonathan Stephens, Holger Prokisch, Wendy Erber, Simon C. Potter, Sarah L. Bray, Philippa Burns, Jennifer Jolley, Mario Falchi, Brigitte Kühnel, Jeanette Erdmann, Heribert Schunkert, Nilesh J. Samani, Thomas IlligStephen F. Garner, Angela Rankin, Christa Meisinger, John R. Bradley, Swee Lay Thein, Alison H. Goodall, Tim D. Spector, Panos Deloukas, Willem H. Ouwehand

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114 Citations (Scopus)

Abstract

Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits.We performed a genomewide 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 ± 0.80 109/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 Gallele 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.

Original language	English
Pages (from-to)	3831-3837
Number of pages	7
Journal	Blood
Volume	113
Issue number	16
DOIs	https://doi.org/10.1182/blood-2008-10-184234
Publication status	Published - 17 Nov 2009
Externally published	Yes

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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., ... Ouwehand, W. H. (2009). Anovel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function. Blood, 113(16), 3831-3837. https://doi.org/10.1182/blood-2008-10-184234

@article{300e988194c24b2f8735547e1871a91c,

title = "Anovel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function",

abstract = "Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits.We performed a genomewide 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 ± 0.80 109/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 Gallele 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.",

author = "Nicole Soranzo and Augusto Rendon and Christian Gieger and Jones, {Chris I.} and Watkins, {Nicholas A.} and Stephan Menzel and Angela D{\"o}ring and Jonathan Stephens and Holger Prokisch and Wendy Erber and Potter, {Simon C.} and Bray, {Sarah L.} and Philippa Burns and Jennifer Jolley and Mario Falchi and Brigitte K{\"u}hnel and Jeanette Erdmann and Heribert Schunkert and Samani, {Nilesh J.} and Thomas Illig and Garner, {Stephen F.} and Angela Rankin and Christa Meisinger and Bradley, {John R.} and Thein, {Swee Lay} and Goodall, {Alison H.} and Spector, {Tim D.} and Panos Deloukas and Ouwehand, {Willem H.}",

year = "2009",

month = nov,

day = "17",

doi = "10.1182/blood-2008-10-184234",

language = "English",

volume = "113",

pages = "3831--3837",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

number = "16",

}

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 2009, 'Anovel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function', Blood, vol. 113, no. 16, pp. 3831-3837. https://doi.org/10.1182/blood-2008-10-184234

TY - JOUR

T1 - Anovel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function

AU - Soranzo, Nicole

AU - Rendon, Augusto

AU - Gieger, Christian

AU - Jones, Chris I.

AU - Watkins, Nicholas A.

AU - Menzel, Stephan

AU - Döring, Angela

AU - Stephens, Jonathan

AU - Prokisch, Holger

AU - Erber, Wendy

AU - Potter, Simon C.

AU - Bray, Sarah L.

AU - Burns, Philippa

AU - Jolley, Jennifer

AU - Falchi, Mario

AU - Kühnel, Brigitte

AU - Erdmann, Jeanette

AU - Schunkert, Heribert

AU - Samani, Nilesh J.

AU - Illig, Thomas

AU - Garner, Stephen F.

AU - Rankin, Angela

AU - Meisinger, Christa

AU - Bradley, John R.

AU - Thein, Swee Lay

AU - Goodall, Alison H.

AU - Spector, Tim D.

AU - Deloukas, Panos

AU - Ouwehand, Willem H.

PY - 2009/11/17

Y1 - 2009/11/17

N2 - Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits.We performed a genomewide 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 ± 0.80 109/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 Gallele 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.

AB - Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits.We performed a genomewide 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 ± 0.80 109/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 Gallele 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.

UR - http://www.scopus.com/inward/record.url?scp=65549162781&partnerID=8YFLogxK

U2 - 10.1182/blood-2008-10-184234

DO - 10.1182/blood-2008-10-184234

M3 - Article

C2 - 19221038

AN - SCOPUS:65549162781

SN - 0006-4971

VL - 113

SP - 3831

EP - 3837

JO - Blood

JF - Blood

IS - 16

ER -

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

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