Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels

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Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels

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Title: Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels
Author: Meyer, Tamra E.; Verwoert, Germaine C.; Hwang, Shih-Jen; Glazer, Nicole L.; Smith, Albert V.; van Rooij, Frank J. A.; Ehret, Georg B.; Boerwinkle, Eric; Felix, Janine F.; Leak, Tennille S.; Harris, Tamara B.; Yang, Qiong; Dehghan, Abbas; Aspelund, Thor; Katz, Ronit; Homuth, Georg; Kocher, Thomas; Rettig, Rainer; Ried, Janina S.; Gieger, Christian; Prucha, Hanna; Pfeufer, Arne; Meitinger, Thomas; Coresh, Josef; Sarnak, Mark J.; Chen, Yii-Der Ida; Uitterlinden, André G.; Chakravarti, Aravinda; Psaty, Bruce M.; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.; Gudnason, Vilmundur; Siscovick, David S.; Köttgen, Anna; Hofman, Albert; Kao, W. H. Linda; Fox, Caroline

Note: Order does not necessarily reflect citation order of authors.

Citation: Meyer, Tamra E., Germaine C. Verwoert, Shih-Jen Hwang, Nicole L. Glazer, Albert V. Smith, Frank J. A. van Rooij, Georg B. Ehret, et al. 2010. Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six loci influencing serum magnesium levels. PLoS Genetics 6(8): e1001045.
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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 \(\sim\)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 \((p<5 \times 10^{-8})\) or suggestive associations \((p<4 \times 10^{-7})\) 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 \((p<4 \times 10^{-7})\). 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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Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10243429
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