A genome-wide association study provides insights into the genetic etiology of 57 essential and non-essential trace elements in humans

Marta R Moksnes; Ailin F Hansen; Brooke N Wolford; Laurent F Thomas; Humaira Rasheed; Anica Simić; Laxmi Bhatta; Anne Lise Brantsæter; Ida Surakka; Wei Zhou; Per Magnus; Pål R Njølstad; Ole A Andreassen; Tore Syversen; Jie Zheng; Lars G Fritsche; David M Evans; Nicole M Warrington; Therese H Nøst; Bjørn Olav Åsvold; Trond Peder Flaten; Cristen J Willer; Kristian Hveem; Ben M Brumpton

doi:10.1038/s42003-024-06101-z

A genome-wide association study provides insights into the genetic etiology of 57 essential and non-essential trace elements in humans

Commun Biol. 2024 Apr 9;7(1):432. doi: 10.1038/s42003-024-06101-z.

Authors

Marta R Moksnes¹, Ailin F Hansen², Brooke N Wolford², Laurent F Thomas^{2

3

4

5}, Humaira Rasheed^{2

6

7}, Anica Simić⁸, Laxmi Bhatta², Anne Lise Brantsæter⁹, Ida Surakka¹⁰, Wei Zhou^{11

12

13}, Per Magnus¹⁴, Pål R Njølstad^{15

16}, Ole A Andreassen^{17

18}, Tore Syversen¹⁹, Jie Zheng^{20

21

22}, Lars G Fritsche^{23

24}, David M Evans^{25

26

27}, Nicole M Warrington^{2

25

26

27}, Therese H Nøst^{2

28}, Bjørn Olav Åsvold^{2

29

30}, Trond Peder Flaten⁸, Cristen J Willer^{2

11

31

32}, Kristian Hveem^{2

29}, Ben M Brumpton^{33

34

35}

Affiliations

¹ HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. marta.r.moksnes@ntnu.no.
² HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
³ Department of Clinical and Molecular Medicine, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
⁴ BioCore-Bioinformatics Core Facility, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
⁵ Clinic of Laboratory Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
⁶ MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁷ Division of Medicine and Laboratory Sciences, University of Oslo, Oslo, Norway.
⁸ Department of Chemistry, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
⁹ Department of Food Safety, Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
¹⁰ Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA.
¹¹ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
¹² Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
¹³ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
¹⁴ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
¹⁵ Mohn Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway.
¹⁶ Children and Youth Clinic, Haukeland University Hospital, Bergen, Norway.
¹⁷ NORMENT Centre, University of Oslo, Oslo, Norway.
¹⁸ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
¹⁹ Department of Neuroscience, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
²⁰ Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
²¹ 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 Jiao Tong University School of Medicine, Shanghai, China.
²² MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Bristol, UK.
²³ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
²⁴ Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
²⁵ Institute for Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
²⁶ Frazer Institute, The University of Queensland, Woolloongabba, QLD, Australia.
²⁷ MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.
²⁸ Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
²⁹ HUNT Research Centre, Department of Public Health and Nursing, NTNU-Norwegian University of Science and Technology, Levanger, Norway.
³⁰ Department of Endocrinology, Clinic of Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
³¹ Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
³² Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
³³ HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. ben.brumpton@ntnu.no.
³⁴ HUNT Research Centre, Department of Public Health and Nursing, NTNU-Norwegian University of Science and Technology, Levanger, Norway. ben.brumpton@ntnu.no.
³⁵ Clinic of Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway. ben.brumpton@ntnu.no.

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.

MeSH terms

Genome-Wide Association Study
Humans
Male
Manganese
Selenium* / analysis
Trace Elements* / metabolism
Zinc

Substances

Trace Elements
Zinc
Selenium
Manganese

Grants and funding

R35 HL135824/HL/NHLBI NIH HHS/United States