A Genome-wide Association Study Identifies Three Loci Associated with Mean Platelet Volume

Meisinger, Christa, Prokisch, Holger, Gieger, Christian, Soranzo, Nicole, Mehta, Divya, Rosskopf, Dieter, Lichtner, Peter, Klopp, Norman, Stephens, Jonathan, Watkins, Nicholas A., Deloukas, Panos, Greinacher, Andreas, Koenig, Wolfgang, Nauck, Mathias, Rimmbach, Christian, Volzke, Henry, Peters, Annette, Illig, Thomas, Ouwehand, Willem H., Meitinger, Thomas, Wichmann, H-Erich and Doring, Angela (2009) A Genome-wide Association Study Identifies Three Loci Associated with Mean Platelet Volume. American Journal of Human Genetics, 84 1: 66-71. doi:10.1016/j.ajhg.2008.11.015


Author Meisinger, Christa
Prokisch, Holger
Gieger, Christian
Soranzo, Nicole
Mehta, Divya
Rosskopf, Dieter
Lichtner, Peter
Klopp, Norman
Stephens, Jonathan
Watkins, Nicholas A.
Deloukas, Panos
Greinacher, Andreas
Koenig, Wolfgang
Nauck, Mathias
Rimmbach, Christian
Volzke, Henry
Peters, Annette
Illig, Thomas
Ouwehand, Willem H.
Meitinger, Thomas
Wichmann, H-Erich
Doring, Angela
Title A Genome-wide Association Study Identifies Three Loci Associated with Mean Platelet Volume
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
1537-6605
Publication date 2009-01-09
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2008.11.015
Open Access Status
Volume 84
Issue 1
Start page 66
End page 71
Total pages 6
Place of publication Cambridge, MA United States
Publisher Cell Press
Collection year 2009
Language eng
Abstract Mean platelet volume (MPV) is increased in myocardial and cerebral infarction and is an independent and strong predictor for postevent morbidity and mortality. We conducted a genome-wide association study (GWAS), the KORA (Kooperative Gesundheitsforschung in der Region Augsburg) F3 500K study, and found MPV to be strongly associated with three common single-nucleotide polymorphisms (SNPs): rs7961894 located within intron 3 of WDR66 on chromosome 12q24.31, rs12485738 upstream of the ARHGEF3 on chromosome 3p13-p21, and rs2138852 located upstream of TAOK1 on chromosome 17q11.2. We replicated all three SNPs in another GWAS from the UK and in two population-based samples from Germany. In a combined analysis including 10,048 subjects, the SNPs had p values of 7.24 × 10-48 for rs7961894, 3.81 × 10-27 for rs12485738, and 7.19 × 10-28 for rs2138852. These three quantitative trait loci together accounted for 4%-5% of the variance in MPV. In-depth sequence analysis of WDR66 in 382 samples from the extremes revealed 20 new variants and a haplotype with three coding SNPs and one SNP at the transcription start site associated with MPV (p = 6.8 × 10-5). In addition, expression analysis indicated a direct correlation of WDR66 transcripts and MPV. These findings may not only enhance our understanding of platelet activation and function, but may also provide a focus for several novel research avenues.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Fri, 24 Oct 2014, 17:11:25 EST by Sylvie Pichelin on behalf of Queensland Brain Institute