Heritability and preliminary genome-wide linkage analysis of arsenic metabolites in urine

Maria Tellez-Plaza, Matthew O. Gribble, V. Saroja Voruganti, Kevin A. Francesconi, Walter Goessler, Jason G. Umans, Ellen K. Silbergeld, Eliseo Guallar, Nora Franceschini, Kari E. North, Wen-Hong Linda Kao, Jean W. MacCluer, Shelley A. Cole, Ana Navas Acien

Research output: Contribution to journalArticlepeer-review


Background: Arsenic (III) methyltransferase (AS3MT) has been related to urine arsenic metabolites in association studies. Other genes might also play roles in arsenic metabolism and excretion. Objective: We evaluated genetic determinants of urine arsenic metabolites in American Indian adults from the Strong Heart Study (SHS). Methods: We evaluated heritability of urine arsenic metabolites [percent inorganic arsenic (%iAs), percent monomethylarsonate (%MMA), and percent dimethylarsinate (%DMA)] in 2,907 SHS participants with urine arsenic measurements and at least one relative within the cohort. We conducted a preliminary linkage analysis in a subset of 487 participants with available genotypes on approximately 400 short tandem repeat markers using a general pedigree variance component approach for localizing quantitative trait loci (QTL). Results: The medians (interquartile ranges) for %iAs, %MMA, and %DMA were 7.7% (5.4-10.7%), 13.6% (10.5-17.1%), and 78.4% (72.5-83.1%), respectively. The estimated heritability was 53% for %iAs, 50% for %MMA, and 59% for %DMA. After adjustment for sex, age, smoking, body mass index, alcohol consumption, region, and total urine arsenic concentrations, LOD [logarithm (to the base of 10) of the odds] scores indicated suggestive evidence for genetic linkage with QTLs influencing urine arsenic metabolites on chromosomes 5 (LOD = 2.03 for %iAs), 9 (LOD = 2.05 for %iAs and 2.10 for %MMA), and 11 (LOD = 1.94 for %iAs). A peak for %DMA on chromosome 10 within 2 Mb of AS3MT had an LOD of 1.80. Conclusions: This population-based family study in American Indian communities supports a genetic contribution to variation in the distribution of arsenic metabolites in urine and, potentially, the involvement of genes other than AS3MT.

Original languageEnglish (US)
Pages (from-to)345-351
Number of pages7
JournalEnvironmental health perspectives
Issue number3
StatePublished - 2013


  • American Indians
  • Arsenic metabolism
  • Arsenic species
  • Determinants
  • Heritability
  • Linkage scan
  • Strong Heart Study

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis


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