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Environ Health. 2017 Jul 18;16(1):75. doi: 10.1186/s12940-017-0283-8.

Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study.

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Department of Public Health Sciences, University of Chicago, 900 E 57th Street, KCBD Bldg Room 6110, Chicago, IL, 60637, USA.
Department of Public Health Sciences, University of Chicago, 900 E 57th Street, KCBD Bldg Room 6110, Chicago, IL, 60637, USA.
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois, Chicago, IL, USA.
University of Chicago Research Bangladesh, Dhaka, Bangladesh.
Department of Medicine, University of Chicago, Chicago, IL, USA.
Department of Human Genetics, University of Chicago, Chicago, IL, USA.
Cancer Research Center, University of Chicago, Chicago, IL, USA.



Exposure to arsenic in drinking water is a global health problem and arsenic-induced skin lesions are hallmark of chronic arsenic toxicity. We and others have reported germline genetic variations as risk factors for such skin lesions. The role of copy number variation (CNV) in the germline DNA in this regard is unknown.


From a large prospectively followed-up cohort, exposed to arsenic, we randomly selected 2171 subjects without arsenic-induced skin lesions at enrollment and genotyped their whole blood DNA samples on Illumina Cyto12v2.1 SNP chips to generate DNA copy number. Participants were followed up every 2 years for a total of 8 years, especially for the development of skin lesions. In Cox regression models, each CNV segment was used as a predictor, accounting for other potential covariates, for incidence of skin lesions.


The presence of genomic deletion(s) in a number of genes (OR5J2, GOLGA6L7P, APBA2, GALNTL5, VN1R31P, PHKG1P2, SGCZ, ZNF658) and lincRNA genes (RP11-76I14.1, CTC-535 M15.2, RP11-73B2.2) were associated with higher risk [HR between 1.67 (CI 1.3-2.1) and 2.15 (CI 1.5-2.9) for different CNVs] for development of skin lesions independent of gender, age, and arsenic exposure. Some deletions had stronger effect in a specific gender (ZNF658 in males, SGCZ in females) and some had stronger effect in higher arsenic exposure (lincRNA CTD-3179P9.1) suggesting a possible gene-environment interaction.


This first genome-wide CNV study in a prospectively followed-up large cohort, exposed to arsenic, suggests that DNA deletion in several genes and lincRNA genes may predispose an individual to a higher risk of development of arsenic-induced skin lesions.


Arsenic; Copy number variation; Gene-environment interaction; Skin lesion; Survival analysis; lincRNA

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