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A meta-analysis and genome-wide association study of platelet count and mean platelet volume in African Americans
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نویسنده
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qayyum r. ,snively b.m. ,ziv e. ,nalls m.a. ,liu y. ,tang w. ,yanek l.r. ,lange l. ,evans m.k. ,ganesh s. ,austin m.a. ,lettre g. ,becker d.m. ,zonderman a.b. ,singleton a.b. ,harris t.b. ,mohler e.r. ,logsdon b.a. ,kooperberg c. ,folsom a.r. ,wilson j.g. ,becker l.c. ,reiner a.p.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 3
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چکیده
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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.
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آدرس
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genestar research program,division of general internal medicine,johns hopkins school of medicine,baltimore,md, United States, department of biostatistical sciences,wake forest school of medicine,winston-salem,nc, United States, department of medicine,university of california san francisco,san francisco,ca, United States, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, department of epidemiology and prevention,division of public health sciences,wake forest university school of medicine,winston-salem,nc, United States, division of epidemiology and community health,university of minnesota school of public health,minneapolis,mn, United States, genestar research program,division of general internal medicine,johns hopkins school of medicine,baltimore,md, United States, department of genetics,school of medicine,the university of north carolina at chapel hill,chapel hill,nc, United States, health disparities research section,clinical research branch,national institute on aging,national institutes of health,baltimore,md, United States, division of cardiology,university of michigan health system,ann arbor,mi, United States, department of epidemiology,university of washington,seattle,wa,united states,division of public health sciences,fred hutchinson cancer research center,seattle,wa, United States, montreal heart institute,montreal, Canada, genestar research program,division of general internal medicine,johns hopkins school of medicine,baltimore,md, United States, laboratory of personality and cognition,national institute on aging,national institutes of health,baltimore,md, United States, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, laboratory for epidemiology,demography,and biometry,national institute on aging,national institutes of health,baltimore,md, United States, department of medicine,university of pennsylvania school of medicine,philadelphia,pa, United States, program in biostatistics and biomathematics,division of public health sciences,fred hutchinson cancer research center,seattle,wa, United States, program in biostatistics and biomathematics,division of public health sciences,fred hutchinson cancer research center,seattle,wa, United States, division of epidemiology and community health,university of minnesota school of public health,minneapolis,mn, United States, department of medicine,university of mississippi medical center,jackson,ms, United States, genestar research program,division of general internal medicine,johns hopkins school of medicine,baltimore,md, United States, department of epidemiology,university of washington,seattle,wa, United States
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Authors
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