title: Genome-wide association study reveals two loci for serum magnesium concentrations in European-American children.
abstract: Magnesium ions are essential to the basic metabolic processes in the human body. Previous genetic studies indicate that serum magnesium levels are highly heritable, and a few genetic loci have been reported involving regulation of serum magnesium in adults. In this study, we examined if additional loci influence serum magnesium levels in children. We performed a genome-wide association study (GWAS) on 2,267 European-American children genotyped on the Illumina HumanHap550 or Quad610 arrays, sharing over 500,000 markers, as the discovery cohort and 257 European-American children genotyped on the Illumina Human OmniExpress arrays as the replication cohort. After genotype imputation, the strongest associations uncovered were with imputed SNPs residing within the FGFR2 (rs1219515, P = 1.1 × 10(-5)) and PAPSS2 (rs1969821, P = 7.2 × 10(-6)) loci in the discovery cohort, both of which were robustly replicated in our independent patient cohort (rs1219515, P = 3.5 × 10(-3); rs1969821, P = 1.2 × 10(-2)). The associations at the FGFR2 locus were also weakly replicated in a dataset from a previous GWAS of serum magnesium in European adults. Our results indicate that FGFR2 and PAPSS2 may play an important role in the regulation of magnesium homeostasis in children of European-American ancestry.
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chang
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Glessner
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, 21205, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Tin
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey, 07102, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wei
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Frank D
authors.initials: FD
authors.lastname: Mentch
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Hou
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Tiancheng
authors.initials: T
authors.lastname: Wang
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Haijun
authors.initials: H
authors.lastname: Qiu
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Kim
authors.affiliation: The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.|Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.|Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
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, 19104, USA.|Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.|Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
mesh_terms: D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008274:Magnesium / Q000097:blood*; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D013430:Sulfate Adenylyltransferase / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics
chemical_list: D009097:Multienzyme Complexes; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; C022322:PAPS synthetase; D013430:Sulfate Adenylyltransferase; D008274:Magnesium