Heritability and Preliminary Genome-Wide Linkage Analysis of Arsenic Metabolites in Urine

Environ Health Perspect. 2013 Mar;121(3):345-51. doi: 10.1289/ehp.1205305. Epub 2013 Jan 15.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arsenic / urine*
  • Female
  • Genetic Linkage*
  • Genome-Wide Association Study*
  • Humans
  • Life Style
  • Male
  • Middle Aged

Substances

  • Arsenic