title: A novel 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 genome-wide 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 10(9)/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 G allele 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.
authors.affiliation: Human Genetics Department, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom. ns6@sanger.ac.uk
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: Augusto
authors.initials: A
authors.lastname: Rendon
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Chris I
authors.initials: CI
authors.lastname: Jones
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Watkins
authors.forename: Stephan
authors.initials: S
authors.lastname: Menzel
authors.forename: Angela
authors.initials: A
authors.lastname: Döring
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stephens
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.forename: Wendy
authors.initials: W
authors.lastname: Erber
authors.forename: Simon C
authors.initials: SC
authors.lastname: Potter
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Bray
authors.forename: Philippa
authors.initials: P
authors.lastname: Burns
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jolley
authors.forename: Mario
authors.initials: M
authors.lastname: Falchi
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kühnel
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Garner
authors.forename: Angela
authors.initials: A
authors.lastname: Rankin
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.forename: John R
authors.initials: JR
authors.lastname: Bradley
authors.forename: Swee Lay
authors.initials: SL
authors.lastname: Thein
authors.forename: Alison H
authors.initials: AH
authors.lastname: Goodall
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics; D034061:Thrombopoiesis / Q000235:genetics*