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

Kyle Dack, Mariona Bustamante, Caroline M. Taylor, Sabrina Llop, Manuel Lozano, Paul D Yousefi, Regina Grazuleviciene, Kristine Bjerve Gutzkow, Anne Lise Brantsæter, Dan Mason, Georgia Escaramís, Sarah J Lewis

Research output: Other contribution

Abstract

Background
Mercury (Hg) is a toxic heavy metal which humans are most commonly exposed to through
food chain contamination, especially via fish consumption. Even low-level exposure can be
harmful because of the poor clearance rate, particularly for methylmercury. It is likely that genetic
variation modifies exposure through changes in the absorption, metabolism, and/or removal of
mercury. Associations have been reported between Hg and variants at multiple genetic loci, but in
many cases these results are not yet replicated.
Methods
This study included two populations: pregnant women from the Avon Longitudinal Study of
Parents and Children (ALSPAC, n=2,893) and children from the Human Early Life Exposome
(HELIX, n=1,042). Genome-wide testing by cohort was performed by fitting linear regressions
models on whole blood Hg levels and Haplotype Reference Consortium imputed single-nucleotide
polymorphisms (SNPs). SNP heritability was estimated using linkage disequilibrium (LD)- score
regression, and the biological functions of the top variants were investigated using resources
which aggregate prior literature.
Results
Hg SNP heritability was estimated to be 24.0% (95% CI: 16.9% to 46.4%) for pregnant
women. The number of genetic variants independently associated with whole blood mercury levels
above a suggestive p-value threshold (P < 1x10-5) was 16 for pregnant women and 21 for children.
However, none were replicated in both populations, nor did any pass a stronger genome-wide
significant threshold (P < 5x10-8). Several suggestive variants had possible biological links to Hg
such as rs146099921 in metal transporter SLC39A14, and two variants (rs28618224, rs7154700)
in potassium voltage-gated channels genes.
Discussion
There was evidence for a considerable proportion of Hg variance being attributed to
genome-wide variation in pregnant women. However, results between pregnant women and
children were highly discordant which could reflect differences in metabolism and a gene-age
interaction with Hg levels. There were a large number of SNPs suggestively associated with Hg
levels, which likely include both true associations and false positives. These interim findings will be
expanded following collaboration with additional study groups.
Original languageEnglish
DOIs
Publication statusPublished - 8 Feb 2023

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