School of Medicine Publications and Presentations
Linkage Analysis of Urine Arsenic Species Patterns in the Strong Heart Family Study
Document Type
Article
Publication Date
11-2015
Abstract
Arsenic toxicokinetics are important for disease risks in exposed populations, but genetic determinants are not fully understood. We examined urine arsenic species patterns measured by HPLC-ICPMS among 2189 Strong Heart Study participants 18 years of age and older with data on ~400 genome-wide microsatellite markers spaced ~10 cM and arsenic speciation (683 participants from Arizona, 684 from Oklahoma, and 822 from North and South Dakota). We logit-transformed % arsenic species (% inorganic arsenic, %MMA, and %DMA) and also conducted principal component analyses of the logit % arsenic species. We used inverse-normalized residuals from multivariable-adjusted polygenic heritability analysis for multipoint variance components linkage analysis. We also examined the contribution of polymorphisms in the arsenic metabolism gene AS3MT via conditional linkage analysis. We localized a quantitative trait locus (QTL) on chromosome 10 (LOD 4.12 for %MMA, 4.65 for %DMA, and 4.84 for the first principal component of logit % arsenic species). This peak was partially but not fully explained by measured AS3MT variants. We also localized a QTL for the second principal component of logit % arsenic species on chromosome 5 (LOD 4.21) that was not evident from considering % arsenic species individually. Some other loci were suggestive or significant for 1 geographical area but not overall across all areas, indicating possible locus heterogeneity. This genome-wide linkage scan suggests genetic determinants of arsenic toxicokinetics to be identified by future fine-mapping, and illustrates the utility of principal component analysis as a novel approach that considers % arsenic species jointly.
Recommended Citation
Gribble, M. O., Voruganti, V. S., Cole, S. A., Haack, K., Balakrishnan, P., Laston, S. L., Tellez-Plaza, M., Francesconi, K. A., Goessler, W., Umans, J. G., Thomas, D. C., Gilliland, F., North, K. E., Franceschini, N., & Navas-Acien, A. (2015). Linkage Analysis of Urine Arsenic Species Patterns in the Strong Heart Family Study. Toxicological sciences : an official journal of the Society of Toxicology, 148(1), 89–100. https://doi.org/10.1093/toxsci/kfv164
Publication Title
Toxicological sciences : an official journal of the Society of Toxicology
DOI
10.1093/toxsci/kfv164
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
© The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.