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

作者：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 Matthias; Rimmbach Christian; Voelzke Henry; Peters Annette; Illig Thomas; Ouwehand Willem H; Meitinger Thomas; Wichmann H Erich; Doering Angela

来源：American Journal of Human Genetics, 2009, 84(1): 66-71.

DOI：10.1016/j.ajhg.2008.11.015

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 x 10(-48) for rs7961894, 3.81 X 10(-27) for rs12485738, and 7.19 x 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 x 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.

• 出版日期2009-1-9
• 单位河北医科大学