Genome-wide association study reveals two loci for serum magnesium concentrations in European-American children

Xiao Chang, Joseph Glessner, Adrienne Tin, Jin Li, Yiran Guo, Zhi Wei, Yichuan Liu, Frank D. Mentch, Cuiping Hou, Yan Zhao, Tiancheng Wang, Haijun Qiu, Cecilia Kim, Patrick M A Sleiman, Hakon Hakonarson

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number18792
JournalScientific Reports
Volume5
DOIs
StatePublished - Dec 21 2015

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Genome-Wide Association Study
Magnesium
Serum
Genetic Loci
Human Body
Single Nucleotide Polymorphism
Homeostasis
Genotype
Ions

ASJC Scopus subject areas

  • General

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Genome-wide association study reveals two loci for serum magnesium concentrations in European-American children. / Chang, Xiao; Glessner, Joseph; Tin, Adrienne; Li, Jin; Guo, Yiran; Wei, Zhi; Liu, Yichuan; Mentch, Frank D.; Hou, Cuiping; Zhao, Yan; Wang, Tiancheng; Qiu, Haijun; Kim, Cecilia; Sleiman, Patrick M A; Hakonarson, Hakon.

In: Scientific Reports, Vol. 5, 18792, 21.12.2015.

Research output: Contribution to journalArticle

Chang, X, Glessner, J, Tin, A, Li, J, Guo, Y, Wei, Z, Liu, Y, Mentch, FD, Hou, C, Zhao, Y, Wang, T, Qiu, H, Kim, C, Sleiman, PMA & Hakonarson, H 2015, 'Genome-wide association study reveals two loci for serum magnesium concentrations in European-American children', Scientific Reports, vol. 5, 18792. https://doi.org/10.1038/srep18792
Chang, Xiao ; Glessner, Joseph ; Tin, Adrienne ; Li, Jin ; Guo, Yiran ; Wei, Zhi ; Liu, Yichuan ; Mentch, Frank D. ; Hou, Cuiping ; Zhao, Yan ; Wang, Tiancheng ; Qiu, Haijun ; Kim, Cecilia ; Sleiman, Patrick M A ; Hakonarson, Hakon. / Genome-wide association study reveals two loci for serum magnesium concentrations in European-American children. In: Scientific Reports. 2015 ; Vol. 5.
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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.",
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