ArticleEnvironmental health perspectives2015
The Genetic Architecture of Arsenic Metabolism Efficiency:A SNP-Based Heritability Study of Bangladeshi Adults.
Article in Environmental health perspectives, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 23 citations in OpenAlex.
- Genetic variation in the FMO and GSTO gene clusters impacts arsenic metabolism in humans.PLoS genetics · 2025Article
- Update of the risk assessment of inorganic arsenic in food.EFSA journal. European Food Safety Authority · 2024Article
- Genetics and Epigenetics of Manganese Toxicity.Current environmental health reports · 2022Review
- Nutrition, one-carbon metabolism and arsenic methylation.Toxicology · 2021Review
- Rare, Protein-Altering Variants inEnvironmental health perspectives · 2021Article
- Genetic Determinants of Reduced Arsenic Metabolism Efficiency in the 10q24.32 Region Are Associated With Reduced AS3MT Expression in Multiple Human Tissue Types.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Mendelian randomization of inorganic arsenic metabolism as a risk factor for hypertension- and diabetes-related traits among adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort.International journal of epidemiology · 2019Article
- Gene-environment interaction and maternal arsenic methylation efficiency during pregnancy.Environment international · 2019Article
- A missense variant in FTCD is associated with arsenic metabolism and toxicity phenotypes in Bangladesh.PLoS genetics · 2019Article
- Nutritional Influences on One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity.Annual review of nutrition · 2018Review
- Ethnic, Geographic, and Genetic Differences in Arsenic Metabolism at Low Arsenic Exposure: A Preliminary Analysis in the Multi-Ethnic Study of Atherosclerosis (MESA).International journal of environmental research and public health · 2018Article
- Association of Cardiometabolic Genes with Arsenic Metabolism Biomarkers in American Indian Communities: The Strong Heart Family Study (SHFS).Environmental health perspectives · 2017Article
- Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2016Article
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12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundConsumption of arsenic-contaminated drinking water adversely affects health. There is interindividual variation in arsenic metabolism efficiency, partially due to genetic variation in the arsenic methyltransferase (AS3MT) gene region.
objectivesThe goal of this study was to assess the overall contribution of genetic factors to variation in arsenic metabolism efficiency, as measured by the relative concentration of dimethylarsinic acid (DMA%) in urine.
methodsUsing data on genome-wide single nucleotide polymorphisms (SNPs) and urinary DMA% for 2,053 arsenic-exposed Bangladeshi individuals, we employed various SNP-based approaches for heritability estimation and polygenic modeling.
resultsUsing data on all participants, the percent variance explained (PVE) for DMA% by all measured and imputed SNPs was 16% (p = 0.08), which was reduced to 5% (p = 0.34) after adjusting for AS3MT SNPs. Using information on close relatives only, the PVE was 63% (p = 0.0002), but decreased to 41% (p = 0.01) after adjusting for AS3MT SNPs. Regional heritability analysis confirmed 10q24.32 (AS3MT) as a major arsenic metabolism locus (PVE = 7%, p = 4.4 × 10(-10)), but revealed no additional regions. We observed a moderate association between a polygenic score reflecting elevated DMA% (composed of thousands of non-AS3MT SNPs) and reduced skin lesion risk in an independent sample (p < 0.05). We observed no associations for SNPs reported in prior candidate gene studies of arsenic metabolism.
conclusionsOur results suggest that there are common variants outside of the AS3MT region that influence arsenic metabolism in Bangladeshi individuals, but the effects of these variants are very weak compared with variants near AS3MT. The high heritability estimates observed using family-based heritability approaches suggest substantial effects for rare variants and/or unmeasured environmental factors.
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