{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:06:32Z","timestamp":1786133192199,"version":"build-2736575974"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>\n                    Magnesium (Mg\n                    <jats:sup>2+<\/jats:sup>\n                    ) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg\n                    <jats:sup>2+<\/jats:sup>\n                    , which is crucial for Mg\n                    <jats:sup>2+<\/jats:sup>\n                    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 Mg\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (\n                    <jats:italic toggle=\"yes\">P=<\/jats:italic>\n                    4.4\u00d710\n                    <jats:sup>\u221213<\/jats:sup>\n                    ) near\n                    <jats:italic toggle=\"yes\">TRPM6<\/jats:italic>\n                    , which encodes an epithelial Mg\n                    <jats:sup>2+<\/jats:sup>\n                    channel, and rs35929 (\n                    <jats:italic toggle=\"yes\">P=<\/jats:italic>\n                    2.1\u00d710\n                    <jats:sup>\u221211<\/jats:sup>\n                    ), a variant of\n                    <jats:italic toggle=\"yes\">ARL15<\/jats:italic>\n                    , 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 Mg\n                    <jats:sup>2+<\/jats:sup>\n                    regulated the expression of the highly conserved\n                    <jats:italic toggle=\"yes\">ARL15<\/jats:italic>\n                    ortholog\n                    <jats:italic toggle=\"yes\">arl15b<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">arl15b<\/jats:italic>\n                    knockdown resulted in renal Mg\n                    <jats:sup>2+<\/jats:sup>\n                    wasting and metabolic disturbances. Finally,\n                    <jats:italic toggle=\"yes\">ARL15<\/jats:italic>\n                    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\u2013environment interaction linking Mg\n                    <jats:sup>2+<\/jats:sup>\n                    deficiency to insulin resistance and obesity.\n                  <\/jats:p>","DOI":"10.1681\/asn.2017030267","type":"journal-article","created":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T09:25:19Z","timestamp":1509528319000},"page":"335-348","source":"Crossref","is-referenced-by-count":39,"title":["Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes"],"prefix":"10.1681","volume":"29","author":[{"given":"Tanguy","family":"Corre","sequence":"first","affiliation":[{"name":"Institute of Social and Preventive Medicine,"},{"name":"Department of Computational Biology, University of Lausanne, Lausanne, Switzerland;"},{"name":"Swiss Institute of Bioinformatics, Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Arjona","sequence":"additional","affiliation":[{"name":"Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Hayward","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Youhanna","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of Z\u00fcrich, Zurich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen H.F.","family":"de Baaij","sequence":"additional","affiliation":[{"name":"Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 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Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Traglia","sequence":"additional","affiliation":[{"name":"Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Harris","sequence":"additional","affiliation":[{"name":"Centre for Cognitive Ageing and Cognitive Epidemiology,"},{"name":"Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and Medical Research Council Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Ulivi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico \u201cBurlo Garofolo,\u201d Trieste, 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Hospital, University of Bern, Bern, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Ehret","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Baptista","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozren","family":"Polasek","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Split, Split, Croatia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Rudan","sequence":"additional","affiliation":[{"name":"Usher Institute of Population Health Sciences and 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