dataset · Figshare · 2025
Colocalization results.
Marie C. Sadler (9649799), Jean-Pierre Ghobril (22755953), Oleg Borisov (2313172), Maïwenn Perrais (22755956), Guglielmo Schiano (5745581), Dusan Petrovic (3511739), Eunji Ha (4739670), Belén Ponte (329454), Yong Li (15029), Zulema Rodriguez-Hernandez (22755959), Menno Pruijm (541636), Daniel Ackermann (541637), Idris Guessous (43509), Silvia Stringhini (120881), Georg Ehret (102101), Tanguy Corre (149851), Bruno Vogt (541641), Pierre-Yves Martin (513939), Halit Ongen (687516), Emmanouil Dermitzakis (667262), Janet E. Williams (8466102), Brenda M. Murdoch (9555350), Michelle K. McGuire (8466108), Courtney L. Meehan (6595868), Sébastien Lenglet (11130369), Katalin Susztak (57344), Julien Vaucher (4478023), Aurélien Thomas (105868), Olivier Devuyst (307583), Anna Köttgen (3111024), Murielle Bochud (93046), Zoltán Kutalik (174641)
Cited by 0Open access
Abstract
<div> Zinc is essential for many physiological processes and its deficiency is highly prevalent worldwide. Its complex homeostasis involves membrane transporters from the SLC39/ZIP and SLC30/ZnT protein families. We conducted a genome-wide association study (GWAS) meta-analysis of urinary zinc levels in three European-ancestry cohorts (N = 10,113), followed by <i>in silico</i> and <i>in vivo</i> studies to elucidate their underlying public health and physiological relevance. We identified eleven genome-wide significant signals with six mapping to SLC39/ZIP and SLC30/ZnT gene regions. The lead signal (rs3008217C>G, p = 2.42E-110) in the <i>SLC30A2</i> gene region which explained 6.1% of urinary zinc variation strongly colocalized with its expression in kidney tubules. Low phenotypic and genetic correlations between plasma and urinary zinc levels indicated distinct genetic regulation. High urinary zinc correlated with an unfavorable cardiometabolic profile, and Mendelian randomization analyses suggested causal roles for diabetes increasing urinary zinc levels, and elevated urinary zinc increasing stroke risk. Analyzing country-level allele frequencies and zinc deficiency prevalences revealed a 3-fold higher genetic zinc excretion risk in sub-Saharan Africa compared to Europe, significantly correlating with nutritional zinc deficiency prevalence. Although mutations in <i>SLC30A2</i> are linked to insufficient zinc in human milk, we found no association with common variants using data generated from 387 mothers. Mice experiments showed that dietary zinc deficiency decreased urinary but not plasma zinc levels, and upregulated kidney <i>Slc30a2</i> expression. This first GWAS on urinary zinc highlights the involvement of zinc transporters in its genetic regulation, as well as its role as a non-invasive biomarker for cardiometabolic diseases. </div>
Cite this paper
(9649799), M. C. S., (22755953), J.-P. G., (2313172), O. B., (22755956), M. P., (5745581), G. S., (3511739), D. P., (4739670), E. H., (329454), B. P., (15029), Y. L., (22755959), Z. R.-H., (541636), M. P., (541637), D. A., (43509), I. G., (120881), S. S., (102101), G. E., (149851), T. C., (541641), B. V., (513939), P.-Y. M., (687516), H. O., . . . (174641), Z. K. (2025). Colocalization results. Figshare. https://doi.org/10.1371/journal.pgen.1011928.s004
(9649799), Marie C. Sadler, et al. “Colocalization results.” Figshare, 2025, https://doi.org/10.1371/journal.pgen.1011928.s004.
(9649799), Marie C. Sadler, Jean-Pierre Ghobril (22755953), Oleg Borisov (2313172), Maïwenn Perrais (22755956), Guglielmo Schiano (5745581), Dusan Petrovic (3511739), Eunji Ha (4739670), et al. 2025. “Colocalization results.” Figshare. https://doi.org/10.1371/journal.pgen.1011928.s004.
(9649799), M.C.S. et al. (2025) ‘Colocalization results’, Figshare. Available at: https://doi.org/10.1371/journal.pgen.1011928.s004.
@misc{96497992025colocalization,
title = {{Colocalization results.}},
author = {(9649799), Marie C. Sadler and (22755953), Jean-Pierre Ghobril and (2313172), Oleg Borisov and (22755956), Maïwenn Perrais and (5745581), Guglielmo Schiano and (3511739), Dusan Petrovic and (4739670), Eunji Ha and (329454), Belén Ponte and (15029), Yong Li and (22755959), Zulema Rodriguez-Hernandez and (541636), Menno Pruijm and (541637), Daniel Ackermann and (43509), Idris Guessous and (120881), Silvia Stringhini and (102101), Georg Ehret and (149851), Tanguy Corre and (541641), Bruno Vogt and (513939), Pierre-Yves Martin and (687516), Halit Ongen and (667262), Emmanouil Dermitzakis and (8466102), Janet E. Williams and (9555350), Brenda M. Murdoch and (8466108), Michelle K. McGuire and (6595868), Courtney L. Meehan and (11130369), Sébastien Lenglet and (57344), Katalin Susztak and (4478023), Julien Vaucher and (105868), Aurélien Thomas and (307583), Olivier Devuyst and (3111024), Anna Köttgen and (93046), Murielle Bochud and (174641), Zoltán Kutalik},
journal = {Figshare},
year = {2025},
doi = {10.1371/journal.pgen.1011928.s004}
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