Genome-wide association study of blood mercury in european pregnant women and children

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• dc.contributor.author Dack, Kyle
• dc.contributor.author Bustamante Pineda, Mariona
• dc.contributor.author Taylor, Caroline M.
• dc.contributor.author Llop, Sabrina
• dc.contributor.author Lozano Relaño, Manuel
• dc.contributor.author Yousefi, Paul
• dc.contributor.author Gražulevičienė, Regina
• dc.contributor.author Gutzkow, Kristine B.
• dc.contributor.author Brantsaeter, Anne Lise
• dc.contributor.author Mason, Dan
• dc.contributor.author Escaramís, Geòrgia
• dc.contributor.author Lewis, Sarah J.
• dc.date.accessioned 2024-06-20T07:04:24Z
• dc.date.available 2024-06-20T07:04:24Z
• dc.date.issued 2023
• dc.description.abstract Mercury has high industrial utility and is present in many products, and environmental contamination and occupational exposure are widespread. There are numerous biological systems involved in the absorption, metabolism, and excretion of Hg, and it is possible that some systems may be impacted by genetic variation. If so, genotype may affect tissue concentrations of Hg and subsequent toxic effects. Genome-wide association testing was performed on blood Hg samples from pregnant women of the Avon Longitudinal Study of Parents and Children (n = 2893) and children of the Human Early Life Exposome (n = 1042). Directly-genotyped single-nucleotide polymorphisms (SNPs) were imputed to the Haplotype Reference Consortium r1.1 panel of whole genotypes and modelled againstlog-transformed Hg. Heritability was estimated using linkage disequilibrium score regression. The heritability of Hg was estimated as 24.0% (95% CI: 16.9% to 46.4%) in pregnant women, but could not be determined in children. There were 16 SNPs associated with Hg in pregnant women above a suggestive p-value threshold (p < 1 × 10-5), and 21 for children. However, no SNP passed this threshold in both studies, and none were genome-wide significant (p < 5 × 10-8). SNP-Hg associations were highly discordant between women and children, and this may reflect differences in metabolism, a gene-age interaction, or dose-response effects. Several suggestive variants had plausible links to Hg metabolism, such as rs146099921 in metal transporter SLC39A14, and two variants (rs28618224, rs7154700) in potassium voltage-gated channel genes. The findings would benefit from external validation, as suggestive results may contain both true associations and false positives.
• dc.description.sponsorship This research was supported by the following sources. K.D. is supported by a Ph.D. studentship from the MRC Integrative Epidemiology Unit at the University of Bristol (faculty matched place for MRC and Peter and Jean James Scholarship). C.M.T. is supported by an MRC Career Development Award (MR/T010010/1). S.J.L. and M.L. were funded by Generalitat Valenciana (GV/2021/111), Ministry of Universities (CAS21/00008 and NextGeneration EU), Instituto de Salud Carlos III (FIS-FEDER: 13/1944, 16/1288, 17/00663 and 19/1338; FIS-FSE: 17/00260; Miguel Servet-FSE: MSII20/0006). P.Y. is supported by the Medical Research Council Integrative Epidemiology Unit at the University of Bristol (MC_UU_00011/5). S.J.L. and P.Y. were supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. ALSPAC: The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and K.D. will serve as guarantor for the contents of this paper. Publication was supported by MRC IEU grant MC_UU_00011/1. A comprehensive list of grant funding is available on the ALSPAC website: http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf; This research was specifically funded by Wellcome Trust Grant (WT088806) [genotyping] and NIHR (NF-SI-0611-10196) [blood samples]. The assays of the maternal blood samples were carried out at the Centers for Disease Control and Prevention with funding from NOAA, and the statistical analyses were carried out in Bristol with funding from NOAA and support from the Intramural Research Program of NIAAA, NIH. HELIX: The study has received funding from the European Community’s Seventh Framework Programme (FP7/2007-206) under grant agreement no 308333 (HELIX project) and the H2020-EU.3.1.2.—Preventing Disease Programme under grant agreement no 874583 (ATHLETE project). The genotyping was supported by the projects PI17/01225 and PI17/01935, funded by the Instituto de Salud Carlos III and co-funded by the European Union (ERDF, “A way to make Europe”) and the Centro Nacional de Genotipado-CEGEN (PRB2-ISCIII). BiB received core infrastructure funding from the Wellcome Trust (WT101597MA) and a joint grant from the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) (MR/N024397/1). INMA data collections were supported by grants from the Instituto de Salud Carlos III (PI16/1288 and PI19/1338), CIBERESP, the Generalitat de Catalunya-CIRIT and the Generalitat Valenciana (CIAICO/2021/132). KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009-single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU-FP7-HEALTH-2012 Proposal No 308333 HELIX), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-15). ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.
• dc.format.mimetype application/pdf
• dc.identifier.citation Dack K, Bustamante M, Taylor CM, Llop S, Lozano M, Yousefi P, et al. Genome-wide association study of blood mercury in european pregnant women and children. Genes (Basel). 2023 Nov 24;14(12):2123. DOI: 10.3390/genes14122123
• dc.identifier.doi http://dx.doi.org/10.3390/genes14122123
• dc.identifier.issn 2073-4425
• dc.identifier.uri http://hdl.handle.net/10230/60529
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof Genes (Basel). 2023 Nov 24;14(12):2123
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/211250
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/226285
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000806-S
• dc.rights © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword ALSPAC
• dc.subject.keyword GWAS
• dc.subject.keyword HELIX
• dc.subject.keyword Blood mercury
• dc.subject.keyword Children
• dc.subject.keyword Pregnancy
• dc.title Genome-wide association study of blood mercury in european pregnant women and children
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion