Genome-wide meta-analysis unravels interactions between magnesium homeostasis and metabolic phenotypes

Tanguy Corre, Francisco J. Arjona, Caroline Hayward, Sonia Youhanna, Jeroen H.F. De Baaij, Hendrica Belge, Nadine Nägele, Huguette Debaix, Maxime G. Blanchard, Michela Traglia, Sarah E. Harris, Sheila Ulivi, Rico Rueedi, David Lamparter, Aurélien Macé, Cinzia Sala, Stefania Lenarduzzi, Belen Ponte, Menno Pruijm, Daniel Ackermann & 21 others Georg Ehret, Daniela Baptista, Ozren Polasek, Igor Rudan, Toby W. Hurd, Nicholas D. Hastie, Veronique Vitart, Geràrd Waeber, Zoltán Kutalik, Sven Bergmann, Rosa Vargas-Poussou, Martin Konrad, Paolo Gasparini, Ian J. Deary, John M. Starr, Daniela Toniolo, Peter Vollenweider, Joost G.J. Hoenderop, René J.M. Bindels, Murielle Bochud, Olivier Devuyst

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Magnesium (Mg2+) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg2+, which is crucial for Mg2+ homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg2+ homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4310213) near TRPM6, which encodes an epithelial Mg2+ channel, and rs35929 (P=2.1310211), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg2+ regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg2+ wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene–environment interaction linking Mg2+ deficiency to insulin resistance and obesity.

Original languageEnglish
Pages (from-to)335-348
Number of pages14
JournalJournal of the American Society of Nephrology
Volume29
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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Magnesium
Meta-Analysis
Homeostasis
Genome
Phenotype
Kidney
Zebrafish
GTP-Binding Proteins
Population
Insulin Resistance
Fasting
Obesity
Fats
Urine
Insulin

ASJC Scopus subject areas

  • Nephrology

Cite this

Corre, T., Arjona, F. J., Hayward, C., Youhanna, S., De Baaij, J. H. F., Belge, H., ... Devuyst, O. (2018). Genome-wide meta-analysis unravels interactions between magnesium homeostasis and metabolic phenotypes. Journal of the American Society of Nephrology, 29(1), 335-348. https://doi.org/10.1681/ASN.2017030267

Genome-wide meta-analysis unravels interactions between magnesium homeostasis and metabolic phenotypes. / Corre, Tanguy; Arjona, Francisco J.; Hayward, Caroline; Youhanna, Sonia; De Baaij, Jeroen H.F.; Belge, Hendrica; Nägele, Nadine; Debaix, Huguette; Blanchard, Maxime G.; Traglia, Michela; Harris, Sarah E.; Ulivi, Sheila; Rueedi, Rico; Lamparter, David; Macé, Aurélien; Sala, Cinzia; Lenarduzzi, Stefania; Ponte, Belen; Pruijm, Menno; Ackermann, Daniel; Ehret, Georg; Baptista, Daniela; Polasek, Ozren; Rudan, Igor; Hurd, Toby W.; Hastie, Nicholas D.; Vitart, Veronique; Waeber, Geràrd; Kutalik, Zoltán; Bergmann, Sven; Vargas-Poussou, Rosa; Konrad, Martin; Gasparini, Paolo; Deary, Ian J.; Starr, John M.; Toniolo, Daniela; Vollenweider, Peter; Hoenderop, Joost G.J.; Bindels, René J.M.; Bochud, Murielle; Devuyst, Olivier.

In: Journal of the American Society of Nephrology, Vol. 29, No. 1, 01.01.2018, p. 335-348.

Research output: Contribution to journalArticle

Corre, T, Arjona, FJ, Hayward, C, Youhanna, S, De Baaij, JHF, Belge, H, Nägele, N, Debaix, H, Blanchard, MG, Traglia, M, Harris, SE, Ulivi, S, Rueedi, R, Lamparter, D, Macé, A, Sala, C, Lenarduzzi, S, Ponte, B, Pruijm, M, Ackermann, D, Ehret, G, Baptista, D, Polasek, O, Rudan, I, Hurd, TW, Hastie, ND, Vitart, V, Waeber, G, Kutalik, Z, Bergmann, S, Vargas-Poussou, R, Konrad, M, Gasparini, P, Deary, IJ, Starr, JM, Toniolo, D, Vollenweider, P, Hoenderop, JGJ, Bindels, RJM, Bochud, M & Devuyst, O 2018, 'Genome-wide meta-analysis unravels interactions between magnesium homeostasis and metabolic phenotypes', Journal of the American Society of Nephrology, vol. 29, no. 1, pp. 335-348. https://doi.org/10.1681/ASN.2017030267
Corre, Tanguy ; Arjona, Francisco J. ; Hayward, Caroline ; Youhanna, Sonia ; De Baaij, Jeroen H.F. ; Belge, Hendrica ; Nägele, Nadine ; Debaix, Huguette ; Blanchard, Maxime G. ; Traglia, Michela ; Harris, Sarah E. ; Ulivi, Sheila ; Rueedi, Rico ; Lamparter, David ; Macé, Aurélien ; Sala, Cinzia ; Lenarduzzi, Stefania ; Ponte, Belen ; Pruijm, Menno ; Ackermann, Daniel ; Ehret, Georg ; Baptista, Daniela ; Polasek, Ozren ; Rudan, Igor ; Hurd, Toby W. ; Hastie, Nicholas D. ; Vitart, Veronique ; Waeber, Geràrd ; Kutalik, Zoltán ; Bergmann, Sven ; Vargas-Poussou, Rosa ; Konrad, Martin ; Gasparini, Paolo ; Deary, Ian J. ; Starr, John M. ; Toniolo, Daniela ; Vollenweider, Peter ; Hoenderop, Joost G.J. ; Bindels, René J.M. ; Bochud, Murielle ; Devuyst, Olivier. / Genome-wide meta-analysis unravels interactions between magnesium homeostasis and metabolic phenotypes. In: Journal of the American Society of Nephrology. 2018 ; Vol. 29, No. 1. pp. 335-348.
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AU - Arjona, Francisco J.

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AU - Youhanna, Sonia

AU - De Baaij, Jeroen H.F.

AU - Belge, Hendrica

AU - Nägele, Nadine

AU - Debaix, Huguette

AU - Blanchard, Maxime G.

AU - Traglia, Michela

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AU - Pruijm, Menno

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AU - Ehret, Georg

AU - Baptista, Daniela

AU - Polasek, Ozren

AU - Rudan, Igor

AU - Hurd, Toby W.

AU - Hastie, Nicholas D.

AU - Vitart, Veronique

AU - Waeber, Geràrd

AU - Kutalik, Zoltán

AU - Bergmann, Sven

AU - Vargas-Poussou, Rosa

AU - Konrad, Martin

AU - Gasparini, Paolo

AU - Deary, Ian J.

AU - Starr, John M.

AU - Toniolo, Daniela

AU - Vollenweider, Peter

AU - Hoenderop, Joost G.J.

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