Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six loci influencing serum magnesium levels

Meyer, TE and Verwoert, GC and Hwang, SJ and Glazer, NL and Smith, AV and van Rooij, FJA and Ehret, GB and Boerwinkle, E and Felix, JF and Leak, TS and Harris, TB and Yang, Q and Dehghan, A and Aspelund, T and Katz, R and Homuth, G and Kocher, T and Rettig, R and Ried, JS and Gieger, C and Prucha, H and Pfeufer, A and Meitinger, T and Coresh, J and Hofman, A and Sarnak, MJ and Chen, YDI and Uitterlinden, AG and Chakravarti, A and Psaty, BM and van Duijn, CM and Linda-Kao, WH and Witteman, JCM and Gudnason, V and Siscovick, DS and Fox, CS and Köttgen, A (2010) Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six loci influencing serum magnesium levels. PLoS Genetics, 6 (8). ISSN 1553-7390

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Abstract

Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using ~2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5×10-8) or suggestive associations (p<4×10-7) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4×10-7. Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Meyer, TE Verwoert, GC Hwang, SJ Glazer, NL Smith, AV van Rooij, FJA Ehret, GB Boerwinkle, E Felix, JF Leak, TS Harris, TB Yang, Q Dehghan, A Aspelund, T Katz, R Homuth, G Kocher, T Rettig, R Ried, JS Gieger, C Prucha, H Pfeufer, A Meitinger, T Coresh, J Hofman, A Sarnak, MJ Chen, YDI Uitterlinden, AG Chakravarti, A Psaty, BM van Duijn, CM Linda-Kao, WH Witteman, JCM Gudnason, V Siscovick, DS Fox, CS Köttgen, A
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Visscher, Peter M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	1 August 2010
Date Type:	Publication
Journal or Publication Title:	PLoS Genetics
Volume:	6
Number:	8
DOI or Unique Handle:	10.1371/journal.pgen.1001045
Schools and Programs:	School of Public Health > Epidemiology
Refereed:	Yes
ISSN:	1553-7390
MeSH Headings:	Adult; Aged; European Continental Ancestry Group--genetics; Female; Genome-Wide Association Study; Humans; Magnesium--blood; Male; Middle Aged; Polymorphism, Single Nucleotide; Potassium--blood; Sodium--blood
Other ID:	NLM PMC2916845
PubMed Central ID:	PMC2916845
PubMed ID:	20700443
Date Deposited:	15 Aug 2012 18:16
Last Modified:	22 Jun 2021 15:55
URI:	http://d-scholarship.pitt.edu/id/eprint/13392

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