title: Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network.
abstract: Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ~16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E-13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E - 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs.
authors: Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ 85724, USA.
authors: Zhao
authors: Z
authors: Chen
authors: Hua
authors: H
authors: Tang
authors: Rehan
authors: R
authors: Qayyum
authors: Ursula M
authors: UM
authors: Schick
authors: Michael A
authors: MA
authors: Nalls
authors: Robert
authors: R
authors: Handsaker
authors: Jin
authors: J
authors: Li
authors: Yingchang
authors: Y
authors: Lu
authors: Lisa R
authors: LR
authors: Yanek
authors: Brendan
authors: B
authors: Keating
authors: Yan
authors: Y
authors: Meng
authors: Frank J A
authors: FJ
authors: van Rooij
authors: Yukinori
authors: Y
authors: Okada
authors: Michiaki
authors: M
authors: Kubo
authors: Laura
authors: L
authors: Rasmussen-Torvik
authors: Margaux F
authors: MF
authors: Keller
authors: Leslie
authors: L
authors: Lange
authors: Michele
authors: M
authors: Evans
authors: Erwin P
authors: EP
authors: Bottinger
authors: Michael D
authors: MD
authors: Linderman
authors: Douglas M
authors: DM
authors: Ruderfer
authors: Hakon
authors: H
authors: Hakonarson
authors: George
authors: G
authors: Papanicolaou
authors: Alan B
authors: AB
authors: Zonderman
authors: Omri
authors: O
authors: Gottesman
authors: Cynthia
authors: C
authors: Thomson
authors: Elad
authors: E
authors: Ziv
authors: Andrew B
authors: AB
authors: Singleton
authors: Ruth J F
authors: RJ
authors: Loos
authors: Patrick M A
authors: PM
authors: Sleiman
authors: Santhi
authors: S
authors: Ganesh
authors: Steven
authors: S
authors: McCarroll
authors: Diane M
authors: DM
authors: Becker
authors: James G
authors: JG
authors: Wilson
authors: Guillaume
authors: G
authors: Lettre
authors: Alexander P
authors: AP
authors: Reiner
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D002648:Child; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D015331:Cohort Studies; D004906:Erythrocyte Count; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D055106:Genome-Wide Association Study; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D055815:Young Adult; D055542:alpha-Globins / Q000235:genetics
chemical_list: D006454:Hemoglobins; D055542:alpha-Globins