title: GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children.
abstract: Hematological traits are important clinical indicators, the genetic determinants of which have not been fully investigated. Common measures of hematological traits include red blood cell (RBC) count, hemoglobin concentration (HGB), hematocrit (HCT), mean corpuscular hemoglobin (MCH), MCH concentration (MCHC), mean corpuscular volume (MCV), platelet count (PLT) and white blood cell (WBC) count. We carried out a genome-wide association study of the eight common hematological traits among 7943 African-American children and 6234 Caucasian children. In African Americans, we report five novel associations of HBE1 variants with HCT and MCHC, the alpha-globin gene cluster variants with RBC and MCHC, and a variant at the ARHGEF3 locus with PLT, as well as replication of four previously reported loci at genome-wide significance. In Caucasians, we report a novel association of variants at the COPZ1 locus with PLT as well as replication of four previously reported loci at genome-wide significance. Extended analysis of an association observed between MCH and the alpha-globin gene cluster variants demonstrated independent effects and epistatic interaction at the locus, impacting the risk of iron deficiency anemia in African Americans with specific genotype states. In summary, we extend the understanding of genetic variants underlying hematological traits based on analyses in African-American children.
authors.affiliation: Center for Applied Genomics, Abramson Research Center and Division of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Glessner
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.forename: Cuiping
authors.initials: C
authors.lastname: Hou
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wei
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bradfield
authors.forename: Frank D
authors.initials: FD
authors.lastname: Mentch
authors.forename: Yiran
authors.initials: Y
authors.lastname: Guo
authors.forename: Cecilia
authors.initials: C
authors.lastname: Kim
authors.forename: Qianghua
authors.initials: Q
authors.lastname: Xia
authors.forename: Rosetta M
authors.initials: RM
authors.lastname: Chiavacci
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Thomas
authors.forename: Haijun
authors.initials: H
authors.lastname: Qiu
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Susan L
authors.initials: SL
authors.lastname: Furth
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Patrick M A
authors.initials: PM
authors.lastname: Sleiman
mesh_terms: D001741:Black or African American / Q000235:genetics*; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D004843:Epistasis, Genetic; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000378:metabolism; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D064067:Rho Guanine Nucleotide Exchange Factors; D044465:White People / Q000235:genetics*; D055542:alpha-Globins / Q000235:genetics
chemical_list: C576601:ARHGEF3 protein, human; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D055542:alpha-Globins