caa a22 4500 445861614 CHVBK 20180317145445.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00439-010-0925-1 doi (NATIONALLICENCE)springer-10.1007/s00439-010-0925-1 Genetic association analysis highlights new loci that modulate hematological trait variation in Caucasians and African Americans [Elektronische Daten] [Ken Lo, James Wilson, Leslie Lange, Aaron Folsom, Geneviève Galarneau, Santhi Ganesh, Struan Grant, Brendan Keating, Steven McCarroll, Emile Mohler III, Christopher O'Donnell, Walter Palmas, Weihong Tang, Russell Tracy, Alexander Reiner, Guillaume Lettre] Red blood cell, white blood cell, and platelet measures, including their count, sub-type and volume, are important diagnostic and prognostic clinical parameters for several human diseases. To identify novel loci associated with hematological traits, and compare the architecture of these phenotypes between ethnic groups, the CARe Project genotyped 49,094 single nucleotide polymorphisms (SNPs) that capture variation in ~2,100 candidate genes in DNA of 23,439 Caucasians and 7,112 African Americans from five population-based cohorts. We found strong novel associations between erythrocyte phenotypes and the glucose-6 phosphate dehydrogenase (G6PD) A-allele in African Americans (rs1050828, P<2.0×10−13, T-allele associated with lower red blood cell count, hemoglobin, and hematocrit, and higher mean corpuscular volume), and between platelet count and a SNP at the tropomyosin-4 (TPM4) locus (rs8109288, P=3.0×10−7 in Caucasians; P=3.0×10−7 in African Americans, T-allele associated with lower platelet count). We strongly replicated many genetic associations to blood cell phenotypes previously established in Caucasians. A common variant of the α-globin (HBA2-HBA1) locus was associated with red blood cell traits in African Americans, but not in Caucasians (rs1211375, P<7×10−8, A-allele associated with lower hemoglobin, mean corpuscular hemoglobin, and mean corpuscular volume). Our results show similarities but also differences in the genetic regulation of hematological traits in European- and African-derived populations, and highlight the role of natural selection in shaping these differences. Springer-Verlag, 2010 Lo Ken Montreal Heart Institute, 5000 Bélanger Street, H1T 1C8, Montreal, QC, Canada aut Wilson James Department of Medicine, G.V. (Sonny) Montgomery V.A. Medical Center and the University of Mississipi Medical Center, 39216, Jackson, MS, USA aut Lange Leslie Department of Genetics, University of North Carolina, 5112 Genetic Medicine Building, 27599-7264, Chapel Hill, NC, USA aut Folsom Aaron Division of Epidemiology and Community Health, University of Minnesota, 55454, Minneapolis, MN, USA aut Galarneau Geneviève Montreal Heart Institute, 5000 Bélanger Street, H1T 1C8, Montreal, QC, Canada aut Ganesh Santhi Division of Cardiovascular Medicine, Department of Internal Medicine, The University of Michigan, 48109, Ann Arbor, MI, USA aut Grant Struan Center for Applied Genomics, Division of Human Genetics, Children's Hospital of Philadelphia Research Institute, 19104, Philadelphia, PA, USA aut Keating Brendan Center for Applied Genomics, Division of Human Genetics, Children's Hospital of Philadelphia Research Institute, 19104, Philadelphia, PA, USA aut McCarroll Steven Department of Genetics, Harvard Medical School, 02115, Boston, MA, USA aut Mohler III Emile Cardiovascular Division, Vascular Medicine Section, Department of Medicine, University of Pennsylvania School of Medicine, 19104, Philadelphia, PA, USA aut O'Donnell Christopher Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI), 20892, Bethesda, MD, USA aut Palmas Walter Department of Medicine, Columbia University, 622 West 168th Street, Ph 9 East, 107, 10032, New York, NY, USA aut Tang Weihong Division of Epidemiology and Community Health, University of Minnesota, 55454, Minneapolis, MN, USA aut Tracy Russell Departments of Pathology and Biochemistry, University of Vermont, 208 S. Park Drive, suite 2, 05446, Colchester, VT, USA aut Reiner Alexander Department of Epidemiology, University of Washington, Box 357236, 98195, Seattle, WA, USA aut Lettre Guillaume Montreal Heart Institute, 5000 Bélanger Street, H1T 1C8, Montreal, QC, Canada aut Human Genetics Springer-Verlag 129/3(2011-03-01), 307-317 0340-6717 129:3<307 2011 129 439 https://doi.org/10.1007/s00439-010-0925-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-010-0925-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lo Ken Montreal Heart Institute, 5000 Bélanger Street, H1T 1C8, Montreal, QC, Canada aut NATIONALLICENCE 700 1- Wilson James Department of Medicine, G.V. (Sonny) Montgomery V.A. Medical Center and the University of Mississipi Medical Center, 39216, Jackson, MS, USA aut NATIONALLICENCE 700 1- Lange Leslie Department of Genetics, University of North Carolina, 5112 Genetic Medicine Building, 27599-7264, Chapel Hill, NC, USA aut NATIONALLICENCE 700 1- Folsom Aaron Division of Epidemiology and Community Health, University of Minnesota, 55454, Minneapolis, MN, USA aut NATIONALLICENCE 700 1- Galarneau Geneviève Montreal Heart Institute, 5000 Bélanger Street, H1T 1C8, Montreal, QC, Canada aut NATIONALLICENCE 700 1- Ganesh Santhi Division of Cardiovascular Medicine, Department of Internal Medicine, The University of Michigan, 48109, Ann Arbor, MI, USA aut NATIONALLICENCE 700 1- Grant Struan Center for Applied Genomics, Division of Human Genetics, Children's Hospital of Philadelphia Research Institute, 19104, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Keating Brendan Center for Applied Genomics, Division of Human Genetics, Children's Hospital of Philadelphia Research Institute, 19104, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- McCarroll Steven Department of Genetics, Harvard Medical School, 02115, Boston, MA, USA aut NATIONALLICENCE 700 1- Mohler III Emile Cardiovascular Division, Vascular Medicine Section, Department of Medicine, University of Pennsylvania School of Medicine, 19104, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- O'Donnell Christopher Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI), 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Palmas Walter Department of Medicine, Columbia University, 622 West 168th Street, Ph 9 East, 107, 10032, New York, NY, USA aut NATIONALLICENCE 700 1- Tang Weihong Division of Epidemiology and Community Health, University of Minnesota, 55454, Minneapolis, MN, USA aut NATIONALLICENCE 700 1- Tracy Russell Departments of Pathology and Biochemistry, University of Vermont, 208 S. Park Drive, suite 2, 05446, Colchester, VT, USA aut NATIONALLICENCE 700 1- Reiner Alexander Department of Epidemiology, University of Washington, Box 357236, 98195, Seattle, WA, USA aut NATIONALLICENCE 700 1- Lettre Guillaume Montreal Heart Institute, 5000 Bélanger Street, H1T 1C8, Montreal, QC, Canada aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/3(2011-03-01), 307-317 0340-6717 129:3<307 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer