Evidence map›Paper›PMID 41325371›Full record

SynthesisPLoS genetics2025

Genetic determinants of zinc homeostasis and its role in cardiometabolic diseases.

Marie C Sadler, Jean-Pierre Ghobril, Oleg Borisov, Maïwenn Perrais, Guglielmo Schiano, Dusan Petrovic, Eunji Ha, Belén Ponte, Yong Li, Zulema Rodriguez-Hernandez and 23 more

Abstract readMeta-Analysis
In one paragraph

Synthesis in PLoS genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

33 authors.

Marie C SadlerDepartment of Epidemiology and Health Systems (DESS), University Center for General Medicine and Public Health (UNISANTE), Lausanne, Switzerland.ORCID https://orcid.org/0000-0002-2599-9207
Jean-Pierre GhobrilDepartment of Epidemiology and Health Systems (DESS), University Center for General Medicine and Public Health (UNISANTE), Lausanne, Switzerland.ORCID https://orcid.org/0009-0000-4773-7833
Oleg BorisovInstitute of Genetic Epidemiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID https://orcid.org/0000-0001-8700-4335
Maïwenn PerraisUnit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland.ORCID https://orcid.org/0009-0008-8834-0611
Guglielmo SchianoInstitute of Physiology, University of Zurich, Zurich, Switzerland.ORCID https://orcid.org/0000-0002-3549-7796
Dusan PetrovicClinSearch, Malako, France.
Eunji HaDepartment of Medicine/Nephrology University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
Belén PonteDepartment of Nephrology and Hypertension, Geneva University Hospitals (HUG), Geneva, Switzerland.
Yong LiInstitute of Genetic Epidemiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Zulema Rodriguez-HernandezInstitute of Genetic Epidemiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Menno PruijmDepartment of Nephrology and Hypertension, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
Daniel AckermannUniversity Clinic for Nephrology and Hypertension, Bern University Hospital and University of Bern, Bern, Switzerland.ORCID https://orcid.org/0000-0003-0550-354X
Idris GuessousDepartment and Division of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland.
Silvia StringhiniDepartment and Division of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland.
Georg EhretDepartment of Cardiology, Geneva University Hospitals (HUG), Geneva, Switzerland.
Tanguy CorreDepartment of Epidemiology and Health Systems (DESS), University Center for General Medicine and Public Health (UNISANTE), Lausanne, Switzerland.
Bruno VogtUniversity Clinic for Nephrology and Hypertension, Bern University Hospital and University of Bern, Bern, Switzerland.
Pierre-Yves MartinDepartment of Nephrology and Hypertension, Geneva University Hospitals (HUG), Geneva, Switzerland.
Halit OngenGenetic Medicine and Development, University of Geneva Medical School-CMU, Geneva, Switzerland.
Emmanouil DermitzakisGenetic Medicine and Development, University of Geneva Medical School-CMU, Geneva, Switzerland.
Janet E WilliamsDepartment of Animal, Veterinary and Food Sciences, University of Idaho, Moscow, Idaho, United States of America.
Brenda M MurdochDepartment of Animal, Veterinary and Food Sciences, University of Idaho, Moscow, Idaho, United States of America.
Michelle K McGuireMargaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, Idaho, United States of America.
Courtney L MeehanDepartment of Anthropology, Washington State University, Pullman, Washington, United States of America.
INSPIRE Consortium
Sébastien LengletUnit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland.
Katalin SusztakDepartment of Medicine/Nephrology University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
Julien VaucherDepartment of Internal Medicine and Specialties, Division of Internal Medicine, Fribourg Hospital and University of Fribourg, Fribourg, Switzerland.
Aurélien ThomasUnit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland.
Olivier DevuystInstitute of Physiology, University of Zurich, Zurich, Switzerland.
Anna KöttgenInstitute of Genetic Epidemiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Murielle BochudDepartment of Epidemiology and Health Systems (DESS), University Center for General Medicine and Public Health (UNISANTE), Lausanne, Switzerland.ORCID https://orcid.org/0000-0002-5727-0218
Zoltán KutalikDepartment of Epidemiology and Health Systems (DESS), University Center for General Medicine and Public Health (UNISANTE), Lausanne, Switzerland.ORCID https://orcid.org/0000-0001-8285-7523

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 in silico and in vivo 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 SLC30A2 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 SLC30A2 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 Slc30a2 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.

Indexed as

Cardiovascular DiseasesCation Transport ProteinsHomeostasisMetabolic DiseasesZincAnimalsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMendelian Randomization AnalysisMicePolymorphism, Single NucleotideCation Transport ProteinsSLC30A2 protein, humanZinc

Identifiers

PMID41325371
PMCPMC12677789

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.