title: A meta-analysis and genome-wide association study of platelet count and mean platelet volume in african americans.
abstract: Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388) with p<5×10(-8) of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value): 6p22 (rs12526480, LRRC16A, p = 9.1×10(-9)), 7q11 (rs13236689, CD36, p = 2.8×10(-9)), 10q21 (rs7896518, JMJD1C, p = 2.3×10(-12)), 11q13 (rs477895, BAD, p = 4.9×10(-8)), and 20q13 (rs151361, SLMO2, p = 9.4×10(-9)). Three of these loci (10q21, 11q13, and 20q13) were replicated in European Americans (N = 14,909) and one (11q13) in Hispanic Americans (N = 3,462). For MPV (N = 4,531), genetic variants in 3 regions were significant at p<5×10(-8), two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24). Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic groups. In addition, we also found one region associated with platelet aggregation that may play a potential role in atherothrombosis.
authors.affiliation: GeneSTAR Research Program, Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Rehan
authors.initials: R
authors.lastname: Qayyum
authors.forename: Beverly M
authors.initials: BM
authors.lastname: Snively
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalls
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.forename: Weihong
authors.initials: W
authors.lastname: Tang
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Yanek
authors.forename: Leslie
authors.initials: L
authors.lastname: Lange
authors.forename: Michele K
authors.initials: MK
authors.lastname: Evans
authors.forename: Santhi
authors.initials: S
authors.lastname: Ganesh
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Austin
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lettre
authors.forename: Diane M
authors.initials: DM
authors.lastname: Becker
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zonderman
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.forename: Emile R
authors.initials: ER
authors.lastname: Mohler
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Logsdon
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Becker
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Reiner
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000235:genetics; D010976:Platelet Count; D020641:Polymorphism, Single Nucleotide