title: Heritability and preliminary genome-wide linkage analysis of arsenic metabolites in urine.
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.
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors: Maria
authors: M
authors: Tellez-Plaza
authors: Matthew O
authors: MO
authors: Gribble
authors: V Saroja
authors: VS
authors: Voruganti
authors: Kevin A
authors: KA
authors: Francesconi
authors: Walter
authors: W
authors: Goessler
authors: Jason G
authors: JG
authors: Umans
authors: Ellen K
authors: EK
authors: Silbergeld
authors: Eliseo
authors: E
authors: Guallar
authors: Nora
authors: N
authors: Franceschini
authors: Kari E
authors: KE
authors: North
authors: Wen H
authors: WH
authors: Kao
authors: Jean W
authors: JW
authors: MacCluer
authors: Shelley A
authors: SA
authors: Cole
authors: Ana
authors: A
authors: Navas-Acien
mesh_terms: D000368:Aged; D001151:Arsenic / Q000652:urine*; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged
chemical_list: D001151:Arsenic