A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.

MedStar author(s):
Citation: Nature Genetics. 41(11):1182-90, 2009 Nov.PMID: 19820697Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Meta-Analysis | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov'tSubject headings: *Blood Cells | *Genome-Wide Association Study | *Genome, Human | Blood Cell Count | Blood Cells/cy [Cytology] | Chromosomes, Human, Pair 12 | Coronary Artery Disease/ge [Genetics] | Genetic Markers | Humans | Polymorphism, Single Nucleotide | Selection, GeneticYear: 2009ISSN:
  • 1546-1718
Name of journal: Nature geneticsAbstract: The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.All authors: Altshuler D, Bradley JR, Bumpstead S, Burnett MS, Burns P, Chen L, Deloukas P, Devaney J, Doring A, Elosua R, Epstein SE, Erber W, Erdmann J, Falchi M, Garner SF, Ghori MJ, Gieger C, Goodall AH, Greinacher A, Gwilliam R, Hakonarson HH, Hall AS, Hammond N, Hengstenberg C, Illig T, Kathiresan S, Knouff CW, Konig IR, Kuhnel B, Laskowski RA, Li M, Mangino M, McPherson R, Meisinger C, Melander O, Menzel S, Mooser V, Nauck M, Nieminen MS, O'Donnell CJ, Ouwehand WH, Peltonen L, Perola M, Potter SC, Prokisch H, Rader DJ, Reilly MP, Rendon A, Rice CM, Roberts R, Salo P, Salomaa V, Samani NJ, Sambrook J, Schreiber S, Schunkert H, Schwartz SM, Serbanovic-Canic J, Sinisalo J, Siscovick DS, Soranzo N, Spector TD, Stark K, Stephens J, Stewart AF, Surakka I, Teumer A, Thein SL, Thompson JR, Tyler-Smith C, Van Heel DA, Voight BF, Volker U, Volzke H, Watkins NA, Wells GA, Wichmann HE, Willenborg C, Wright B, Xue YFiscal year: FY2009Digital Object Identifier: Date added to catalog: 2016-01-15
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Journal Article MedStar Authors Catalog Article 19820697 Available 19820697

The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.

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