title: A genome-wide association study identifies three loci associated with mean platelet volume.
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 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.
authors.affiliation: Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: Divya
authors.initials: D
authors.lastname: Mehta
authors.forename: Dieter
authors.initials: D
authors.lastname: Rosskopf
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stephens
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Watkins
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Matthias
authors.initials: M
authors.lastname: Nauck
authors.forename: Christian
authors.initials: C
authors.lastname: Rimmbach
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Angela
authors.initials: A
authors.lastname: Döring
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000166:cytology*; D048429:Cell Size; D002877:Chromosomes, Human / Q000235:genetics*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult