Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 1TH, UK.
ISGlobal, Institute for Global Health, 08036 Barcelona, Spain.
Genes (Basel). 2023 Nov 24;14(12):2123. doi: 10.3390/genes14122123.
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 ( = 2893) and children of the Human Early Life Exposome ( = 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 -value threshold ( < 1 × 10), and 21 for children. However, no SNP passed this threshold in both studies, and none were genome-wide significant ( < 5 × 10). 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.
汞具有很高的工业用途，存在于许多产品中，因此环境污染和职业暴露很普遍。许多生物系统参与汞的吸收、代谢和排泄，其中一些系统可能受到遗传变异的影响。如果是这样，基因型可能会影响组织中汞的浓度和随后的毒性作用。对孕妇（Avon Longitudinal Study of Parents and Children，n = 2893）和儿童（Human Early Life Exposome，n = 1042）的血液汞样本进行了全基因组关联测试。直接基因型的单核苷酸多态性（SNP）被推断为 Haplotype Reference Consortium r1.1 全基因型面板，并针对 log 转换后的 Hg 进行建模。使用连锁不平衡评分回归估计遗传力。孕妇血液中 Hg 的遗传力估计为 24.0%（95%CI：16.9%至 46.4%），但在儿童中无法确定。在孕妇中，有 16 个 SNP 与 Hg 相关，其 < 1 × 10 的提示值阈值，在儿童中，有 21 个 SNP 与之相关。然而，在两项研究中都没有 SNP 通过该阈值，也没有 SNP 在全基因组范围内达到显著水平（ < 5 × 10）。在女性和儿童中，SNP-Hg 关联高度不一致，这可能反映了代谢、基因年龄相互作用或剂量反应效应的差异。一些提示性变体与汞代谢有明显的联系，例如金属转运蛋白 SLC39A14 中的 rs146099921，以及钾电压门控通道基因中的两个变体（rs28618224、rs7154700）。由于提示性结果可能包含真实关联和假阳性，因此这些发现需要外部验证。
