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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.

SUBMITTER: Qayyum R

PROVIDER: S-EPMC3299192 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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A meta-analysis and genome-wide association study of platelet count and mean platelet volume in african americans.

Qayyum Rehan R Snively Beverly M BM Ziv Elad E Nalls Michael A MA Liu Yongmei Y Tang Weihong W Yanek Lisa R LR Lange Leslie L Evans Michele K MK Ganesh Santhi S Austin Melissa A MA Lettre Guillaume G Becker Diane M DM Zonderman Alan B AB Singleton Andrew B AB Harris Tamara B TB Mohler Emile R ER Logsdon Benjamin A BA Kooperberg Charles C Folsom Aaron R AR Wilson James G JG Becker Lewis C LC Reiner Alexander P AP

PLoS genetics 20120308 3

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 ...[more]

PMID: 22423221

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Project description:BackgroundPreeclampsia (PE) is a pregnancy-specific disorder characterized by endothelial dysfunction, and activation of the coagulation system. Alteration of PLT parameters is the common hematological abnormality observed in women with PE. The main aim of this study was to systematically review previous studies from around the world to generate evidence about the relationship between platelet count (PC) and PE, as well as mean platelet volume (MPV) and PE, by calculating the pooled weighted mean difference (WMD) of PC and MPV between PE and normotensive (NT) groups.MethodsRelevant articles which were published in the English language from January 10, 2011, to January 10, 2021, were systematically searched through PubMed, Web of Science, and African journals online. In addition, reference probing of published articles searching was employed through Google Scholar and Google for searching grey literature. The methodological qualities of articles were assessed using Joana Brigg's institute critical appraisal checklist. A random-effects model was used to estimate pooled WMD of PLT parameters between the two groups with the respective 95% confidence intervals (CI) using Stata version 11.0. The I2 statistics and Egger's regression test were used to assess heterogeneity and publication bias among included studies, respectively.ResultsA total of 25 articles were included in this systematic review and meta-analysis. Of which, 23 studies were used in each PC and MPV analysis. The overall pooled WMD of PC and MPV between PE and NT groups were -41.45 × 109/L [95% CI; -51.8, -31.0] and 0.98 fl [95% CI; 0.8, 1.1], respectively. The pooled WMD revealed that PC decreased significantly in the PE group compared to the NT group while MPV increased significantly in the PE group.ConclusionsThis systematic review and meta-analysis indicated that there is a significant decrease in PC and a significant increase in MPV during PE development among pregnant women. As a result, a change in these parameters among pregnant women may indicate the development of PE.

Project description:IntroductionSepsis is a public health problem due to its high prevalence and mortality. Mean platelet volume (MPV), a biomarker reported in routine blood counts, has been investigated and shows promise for determining fatal outcomes in septic patients.ObjectiveEvaluate whether the mean platelet volume (MPV) and mean platelet volume-to-platelet count (MPV/P) ratio are predictors of clinical severity and mortality in patients with sepsis.MethodsA prospective population cohort of 163 patients aged 18-97 years was recruited at the Intensive Care Unit of Pablo Arturo Hospital, Quito, Ecuador from 2017-2019 and followed up for 28 days. Patients were diagnosed with sepsis based on SEPSIS-3 septic shock criteria; in which the MPV and the MPV/P ratio were measured on days 1, 2, and 3. Sequential organ failure assessment (SOFA) score and presence of septic shock assessed clinical severity. Mortality on day 28 was considered the fatal outcome.ResultsThe average age of the patients was 61,15 years (SD 20,94) and female sex was predominant. MPV cutoff points at days 1, 2 and 3 were >9,45fL, >8,95fL and >8, 85fL; and (MPV/P) ratio >8, 18, >4, 12 y >3, 95, respectively. MPV at days 2 (9,85fL) and 3 (8,55fL) and (MPV/P) ratio at days 1 (4,42), 2 (4,21), and 3 (8,55), were predictors of clinical severity assessed by septic shock, which reached significance in the ROC curves. MPV and (MPV/P) ratio were also predictors of clinical severity determined by SOFA at days 1, 2, and 3, where higher values were observed in non-survivors reaching significance in all categories. MPV and MPV/P ratio at days 1, 2 and 3 were independent predictor factors of mortality using Cox proportional hazards model (HR 2,31; 95% CI 1,36-3,94), (HR 2,11; 95% CI 1,17-3,82), (HR 2,13; 95% CI 1,07-4,21) and (HR 2,38; 95% CI 1,38-4,12), (HR 2,15; 95% CI 1,14-4,06), (HR 4,43; 95% CI, 1,72-11,37) respectively.ConclusionsMPV and the MPV/P ratio are predictors of clinical severity and mortality in sepsis. The MPV and its coefficient are indicators of the biological behavior of platelets in sepsis. They should be considered as a cost-effective and rapidly available tool that guides the treatment.

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A meta-analysis and genome-wide association study of platelet count and mean platelet volume in african americans.

Publications

A meta-analysis and genome-wide association study of platelet count and mean platelet volume in african americans.

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