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首页> 外文期刊>Human Molecular Genetics >Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study
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Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

机译:非裔美国人中遗传变异与收缩压和舒张压的关联:候选基因协会资源研究

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The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.
机译:非裔美国人(AA)的高血压患病率高于其他美国人群;然而,很少有人在机管局进行全基因组关联研究(GWAS)。在欧洲血统的人中,GWAS在13个基因座上鉴定出与血压有关的遗传变异。尚不清楚这些变体是否会给非洲血统的人们带来敏感性。在这里,我们使用由8591 AA组成的候选基因关联资源(CARe)联盟检查了全基因组和候选基因与收缩压(SBP)和舒张压(DBP)的关联。基因型包括利用Affymetrix 6.0阵列和250万个HapMap SNP进行插补的全基因组单核苷酸多态性(SNP)数据和利用50K心血管基因中心阵列(ITMAT-Broad-CARe [IBC]阵列)的候选基因SNP数据。对于Affymetrix数据,DBP的最强信号是位于GPR98和ARRDC3附近的rs10474346(P = 3.6×10 -8 )。对于SBP,最强的信号是C21orf91中的rs2258119(P = 4.7×10 -8 )。 SBP的最高IBC关联在SLC25A42附近为rs2012318(P = 6.4×10 −6 ),而DBP的HBC-附近是rs2523586(P = 1.3×10 −6 )。 B.顶级变种均未在其他AA(n = 11882)或欧美(n = 69899)队列中复制。我们在AA样本中复制了先前报道的欧美血压SNP(SH2B3,P = 0.009; TBX3-TBX5,P = 0.03; CSK-ULK3,P = 0.0004)。这些遗传基因座是迄今为止对AA中SBP和DBP遗传影响的最佳证据。更广泛地说,这项工作支持以下观点:AA中的血压是具有遗传基础但又非常复杂的特征。

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  • 来源
    《Human Molecular Genetics 》 |2011年第11期| p.2273-2284| 共12页
  • 作者单位

    Department of Medicine and;

    Department of Medicine,|Department of Epidemiology and;

    Department of Epidemiology and Biostatistics and;

    Department of Medicine and;

    The Institute for Translational Medicine and Therapeutics and;

    Department of Medicine and;

    Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA,;

    Division of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas at Houston, Houston, TX, USA,;

    Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, MI, USA,;

    Medical College of Georgia, Agusta, GA, USA,;

    Department of Medicine, Boston University School of Medicine, Framingham, MA, USA,;

    Department of Radiology, Tufts-New England Medical Center, Boston, MA, USA,;

    Division of Epidemiology and Clinical Applications and;

    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA,;

    Broad Institute of MIT and Harvard, Cambridge, MA, USA,;

    Division of Clinical Epidemiology, Case Western Reserve University, Cleveland, OH, USA,;

    Center for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MA, USA,;

    Department of Genetics, Children's Hospital Boston, Boston, MA, USA,;

    Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA,;

    School of Nursing, University of Mississippi Medical Center, Jackson, MS, USA,;

    Department of Medicine and;

    Department of Medicine, Columbia University, New York, NY, USA,;

    Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA,;

    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA,;

    Center for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MA, USA,;

    Department of Epidemiology and Preventive Medicine, Stritch School of Medicine, Loyola University, Maywood, IL, USA,;

    Department of Medicine and;

    Department of Genetics, Children's Hospital Boston, Boston, MA, USA,;

    Department of Epidemiology and Biostatistics and;

    Center for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MA, USA,;

    Department of Epidemiology and Preventive Medicine, Stritch School of Medicine, Loyola University, Maywood, IL, USA,;

    UNC Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,;

    Pacific Health Research Institute, Honolulu, HI, USA,;

    Division of Cardiology, George Washington University, Washington, DC, USA,;

    Division of Biology and Medicine, Brown University, Providence, RI, USA,;

    Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA,;

    Department of Medicine and;

    Clinical Pharmacology and The Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK and;

    Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA,|Department of Cardiology, Geneva University Hospital, Geneva, Switzerland;

    Clinical Pharmacology and The Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK and;

    Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA,;

    Department of Epidemiology and Biostatistics and;

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