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

doi:10.1038/srep18792

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

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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.

Original language	English (US)
Article number	18792
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep18792
State	Published - Dec 21 2015
Externally published	Yes

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@article{bdf6ae0c98094fea83f5bc7ce6553726,

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.",

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

note = "Funding Information: We thank the patients and their families for their participation in the study. The study was funded by an Institutional Development Fund from The Children{\textquoteright}s Hospital of Philadelphia and by a donation from the Kubert Estate Family.",

year = "2015",

month = dec,

day = "21",

doi = "10.1038/srep18792",

language = "English (US)",

volume = "5",

journal = "Scientific reports",

issn = "2045-2322",

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T1 - Genome-wide association study reveals two loci for serum magnesium concentrations in European-American children

AU - Chang, Xiao

AU - Glessner, Joseph

AU - Tin, Adrienne

AU - Li, Jin

AU - Guo, Yiran

AU - Wei, Zhi

AU - Liu, Yichuan

AU - Mentch, Frank D.

AU - Hou, Cuiping

AU - Zhao, Yan

AU - Wang, Tiancheng

AU - Qiu, Haijun

AU - Kim, Cecilia

AU - Sleiman, Patrick M.A.

AU - Hakonarson, Hakon

N1 - Funding Information: We thank the patients and their families for their participation in the study. The study was funded by an Institutional Development Fund from The Children’s Hospital of Philadelphia and by a donation from the Kubert Estate Family.

PY - 2015/12/21

Y1 - 2015/12/21

N2 - 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.

AB - 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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VL - 5

JO - Scientific reports

JF - Scientific reports

M1 - 18792

ER -

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

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