title: Genome-wide association study of serum minerals levels in children of different ethnic background.
abstract: Calcium, magnesium, potassium, sodium, chloride and phosphorus are the major dietary minerals involved in various biological functions and are commonly measured in the blood serum. Sufficient mineral intake is especially important for children due to their rapid growth. Currently, the genetic mechanisms influencing serum mineral levels are poorly understood, especially for children. We carried out a genome-wide association (GWA) study on 5,602 European-American children and 4,706 African-American children who had mineral measures available in their electronic medical records (EMR). While no locus met the criteria for genome-wide significant association, our results demonstrated a nominal association of total serum calcium levels with a missense variant in the calcium -sensing receptor (CASR) gene on 3q13 (rs1801725, P = 1.96 × 10(-3)) in the African-American pediatric cohort, a locus previously reported in Caucasians. We also confirmed the association result in our pediatric European-American cohort (P = 1.38 × 10(-4)). We further replicated two other loci associated with serum calcium levels in the European-American cohort (rs780094, GCKR, P = 4.26 × 10(-3); rs10491003, GATA3, P = 0.02). In addition, we replicated a previously reported locus on 1q21, demonstrating association of serum magnesium levels with MUC1 (rs4072037, P = 2.04 × 10(-6)). Moreover, in an extended gene-based association analysis we uncovered evidence for association of calcium levels with the previously reported gene locus DGKD in both European-American children and African-American children. Taken together, our results support a role for CASR and DGKD mediated calcium regulation in both African-American and European-American children, and corroborate the association of calcium levels with GCKR and GATA3, and the association of magnesium levels with MUC1 in the European-American children.
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chang
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey, United States of America.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wei
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Frank D
authors.initials: FD
authors.lastname: Mentch
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Hou
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Haijun
authors.initials: H
authors.lastname: Qiu
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Kim
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Patrick M A
authors.initials: PM
authors.lastname: Sleiman
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
mesh_terms: D001741:Black or African American; D002648:Child; D055106:Genome-Wide Association Study; D006801:Humans; D008903:Minerals / Q000097:blood*; D044465:White People
chemical_list: D008903:Minerals