{"doi":"10.1101/2023.02.06.23285518","title":"Genome-wide association study of blood mercury in European pregnant women and children","abstract":"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 < 1×10 −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 < 5×10 −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.","journal":"medRxiv","year":2023,"id":398423,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":16413,"name":"Mariona Bustamante","orcid":"0000-0003-0127-2860","position":1,"is_corresponding":false},{"id":950163,"name":"Caroline M. Taylor","orcid":"0000-0001-8347-5092","position":2,"is_corresponding":false},{"id":714503,"name":"Sabrina Llop","orcid":"0000-0002-6784-4211","position":3,"is_corresponding":false},{"id":714496,"name":"Manuel Lozano","orcid":"0000-0003-2046-5959","position":4,"is_corresponding":false},{"id":282189,"name":"Paul Yousefi","orcid":"0000-0003-3284-3240","position":5,"is_corresponding":false},{"id":237197,"name":"Regina Gražulevičienė","orcid":"0000-0002-0210-8053","position":6,"is_corresponding":false},{"id":270426,"name":"Kristine B. Gützkow","orcid":"0000-0002-6716-5921","position":7,"is_corresponding":false},{"id":392766,"name":"Anne Lise Brantsæter","orcid":"0000-0001-6315-7134","position":8,"is_corresponding":false},{"id":424646,"name":"Dan Mason","orcid":"0000-0002-0026-9216","position":9,"is_corresponding":false},{"id":14356,"name":"Geòrgia Escaramís","orcid":"0000-0002-5416-3177","position":10,"is_corresponding":false},{"id":49712,"name":"Sarah J. Lewis","orcid":"0000-0003-4311-6890","position":11,"is_corresponding":false},{"id":1126408,"name":"Kyle Dack","orcid":"0000-0003-0319-590X","position":0,"is_corresponding":true}],"reference_count":111,"raw_metadata":null,"created_at":"2026-07-19T01:19:47.744358Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}