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. © 2009 The American Society of Human Genetics.
CITATION STYLE
Meisinger, C., Prokisch, H., Gieger, C., Soranzo, N., Mehta, D., Rosskopf, D., … Döring, A. (2009). A Genome-wide Association Study Identifies Three Loci Associated with Mean Platelet Volume. American Journal of Human Genetics, 84(1), 66–71. https://doi.org/10.1016/j.ajhg.2008.11.015
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