Abstract

Trace elements are important for human health but may exert toxic or adverse effects. Mechanisms of uptake, distribution, metabolism, and excretion are partly under genetic control but have not yet been extensively mapped. Here we report a comprehensive multi-element genome-wide association study of 57 essential and non-essential trace elements. We perform genome-wide association meta-analyses of 14 trace elements in up to 6564 Scandinavian whole blood samples, and genome-wide association studies of 43 trace elements in up to 2819 samples measured only in the Trøndelag Health Study (HUNT). We identify 11 novel genetic loci associated with blood concentrations of arsenic, cadmium, manganese, selenium, and zinc in genome-wide association meta-analyses. In HUNT, several genome-wide significant loci are also indicated for other trace elements. Using two-sample Mendelian randomization, we find several indications of weak to moderate effects on health outcomes, the most precise being a weak harmful effect of increased zinc on prostate cancer. However, independent validation is needed. Our current understanding of trace element-associated genetic variants may help establish consequences of trace elements on human health.

A genome-wide association study of 57 trace elements measured in up to 6564 Scandinavians, identifies genetic loci associated with blood levels of essential and non-essential trace elements and explores their effects on health outcomes.

Details

Title
A genome-wide association study provides insights into the genetic etiology of 57 essential and non-essential trace elements in humans
Author
Moksnes, Marta R. 1   VIAFID ORCID Logo  ; Hansen, Ailin F. 1 ; Wolford, Brooke N. 1   VIAFID ORCID Logo  ; Thomas, Laurent F. 2   VIAFID ORCID Logo  ; Rasheed, Humaira 3   VIAFID ORCID Logo  ; Simić, Anica 4 ; Bhatta, Laxmi 1 ; Brantsæter, Anne Lise 5   VIAFID ORCID Logo  ; Surakka, Ida 6 ; Zhou, Wei 7   VIAFID ORCID Logo  ; Magnus, Per 8 ; Njølstad, Pål R. 9   VIAFID ORCID Logo  ; Andreassen, Ole A. 10   VIAFID ORCID Logo  ; Syversen, Tore 11 ; Zheng, Jie 12   VIAFID ORCID Logo  ; Fritsche, Lars G. 13   VIAFID ORCID Logo  ; Evans, David M. 14   VIAFID ORCID Logo  ; Warrington, Nicole M. 15   VIAFID ORCID Logo  ; Nøst, Therese H. 16 ; Åsvold, Bjørn Olav 17   VIAFID ORCID Logo  ; Flaten, Trond Peder 4   VIAFID ORCID Logo  ; Willer, Cristen J. 18   VIAFID ORCID Logo  ; Hveem, Kristian 19 ; Brumpton, Ben M. 20   VIAFID ORCID Logo 

1  NTNU—Norwegian University of Science and Technology, HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393) 
2  NTNU—Norwegian University of Science and Technology, HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); NTNU—Norwegian University of Science and Technology, Department of Clinical and Molecular Medicine, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); NTNU—Norwegian University of Science and Technology, BioCore—Bioinformatics Core Facility, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); Trondheim University Hospital, Clinic of Laboratory Medicine, St. Olav’s Hospital, Trondheim, Norway (GRID:grid.52522.32) (ISNI:0000 0004 0627 3560) 
3  NTNU—Norwegian University of Science and Technology, HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); University of Bristol, MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Oslo, Division of Medicine and Laboratory Sciences, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921) 
4  NTNU—Norwegian University of Science and Technology, Department of Chemistry, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393) 
5  Norwegian Institute of Public Health, Department of Food Safety, Division of Climate and Environmental Health, Oslo, Norway (GRID:grid.418193.6) (ISNI:0000 0001 1541 4204) 
6  University of Michigan, Department of Internal Medicine, Division of Cardiology, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000 0004 1936 7347) 
7  University of Michigan, Department of Computational Medicine and Bioinformatics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000 0004 1936 7347); Massachusetts General Hospital, Analytic and Translational Genetics Unit, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Broad Institute of Harvard and MIT, Program in Medical and Population Genetics, Cambridge, USA (GRID:grid.66859.34) (ISNI:0000 0004 0546 1623) 
8  Norwegian Institute of Public Health, Centre for Fertility and Health, Oslo, Norway (GRID:grid.418193.6) (ISNI:0000 0001 1541 4204) 
9  University of Bergen, Mohn Center for Diabetes Precision Medicine, Department of Clinical Science, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443); Haukeland University Hospital, Children and Youth Clinic, Bergen, Norway (GRID:grid.412008.f) (ISNI:0000 0000 9753 1393) 
10  University of Oslo, NORMENT Centre, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Oslo University Hospital, Division of Mental Health and Addiction, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
11  NTNU—Norwegian University of Science and Technology, Department of Neuroscience, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393) 
12  Shanghai Jiao Tong University School of Medicine, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293); Shanghai Jiao Tong University School of Medicine, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Shanghai Digital Medicine Innovation Center, Ruijin Hospital, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293); University of Bristol, MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
13  University of Michigan School of Public Health, Department of Biostatistics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000 0004 1936 7347); University of Michigan School of Public Health, Center for Statistical Genetics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000 0004 1936 7347) 
14  The University of Queensland, Institute for Molecular Biosciences, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); The University of Queensland, Frazer Institute, Woolloongabba, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); University of Bristol, MRC Integrative Epidemiology Unit (IEU), Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
15  NTNU—Norwegian University of Science and Technology, HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); The University of Queensland, Institute for Molecular Biosciences, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); The University of Queensland, Frazer Institute, Woolloongabba, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); University of Bristol, MRC Integrative Epidemiology Unit (IEU), Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
16  NTNU—Norwegian University of Science and Technology, HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); UiT The Arctic University of Norway, Department of Community Medicine, Tromsø, Norway (GRID:grid.10919.30) (ISNI:0000 0001 2259 5234) 
17  NTNU—Norwegian University of Science and Technology, HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); NTNU—Norwegian University of Science and Technology, HUNT Research Centre, Department of Public Health and Nursing, Levanger, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); Trondheim University Hospital, Department of Endocrinology, Clinic of Medicine, St. Olav’s Hospital, Trondheim, Norway (GRID:grid.52522.32) (ISNI:0000 0004 0627 3560) 
18  NTNU—Norwegian University of Science and Technology, HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); University of Michigan, Department of Computational Medicine and Bioinformatics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000 0004 1936 7347); University of Michigan, Division of Cardiovascular Medicine, Department of Internal Medicine, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000 0004 1936 7347); University of Michigan, Department of Human Genetics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000 0004 1936 7347) 
19  NTNU—Norwegian University of Science and Technology, HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); NTNU—Norwegian University of Science and Technology, HUNT Research Centre, Department of Public Health and Nursing, Levanger, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393) 
20  NTNU—Norwegian University of Science and Technology, HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); NTNU—Norwegian University of Science and Technology, HUNT Research Centre, Department of Public Health and Nursing, Levanger, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); Trondheim University Hospital, Clinic of Medicine, St. Olav’s Hospital, Trondheim, Norway (GRID:grid.52522.32) (ISNI:0000 0004 0627 3560) 
Pages
432
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-024-06101-z
ProQuest document ID
3034864737
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.