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 H. Kao, Jean W. MacCluer, Shelley A. Cole, Ana Navas-Acien

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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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