2.1 Cross-sectional study
A cross-sectional survey was conducted in Shimen county during November
2016. Residents from three villages in the mining region were recruited
through cluster sampling. Details can be found in our previous
publications11 12. In brief, demographic information,
behavioral characteristics with respect to bath and skin care, history
of diseases and medications, and history of occupational arsenic
exposure were inquired through a face-to-face questionnaire interview.
Height, weight, and waist circumference were measured using a
standardized procedure. Body mass index (BMI) was calculated as weight
[kg] / (height [m])2.
Skin examinations were performed by certificated dermatologists from
Xiangya Hospital, Central South University. Skin disorders were
diagnosed according to skin lesions and symptoms, and dermatoscope or
skin biopsy when necessary. Participants were asked to record their
current intensity of itch on a numerical rating scale (NRS) from 0 to
10. Participants were grouped by NRS: no itch or mild itch (0–2),
moderate itch (3–6), and severe itch (7–10) in data
analysis13.
2.2 Mendelian randomization
study
To confirm the causal relationship between arsenic exposure and
pruritus, we conducted a Mendelian randomization (MR) analysis using
external data from the UK Biobank, a prospective cohort that recruited
500,000 participants in the United Kingdom during 2007 and 2010. The
percentages of monomethylated arsenic (MMA%) and dimethylated arsenic
(DMA%) in total urinary arsenic are established indicators for the
toxicity of arsenic, as high MMA% and low DMA% represent insufficient
detoxication and vulnerability to arsenic exposure. Therefore, we
constructed the polygenic risk scores (PRSs) for MMA% and DMA%
according to a published genome-wide association study (GWAS) using data
on urinary arsenic metabolite concentrations and genome-wide single
nucleotide polymorphisms (SNPs) from 1,313 arsenic-exposed
individuals14. They identified significant
associations (P <5×10–8) for both
MMA% and DMA% near the AS3MT gene (arsenite methyltransferase;
10q24.32), with five SNPs showing independent associations. The number
of alleles (0, 1, or 2) for each individual was then summed after
multiplication with the β coefficients between the SNPs and MMA% or
DMA% to derive the PRSMMA% and
PRSDMA% for each participant in the UK Biobank. The
outcome variable was the diagnosis of pruritus from either primary care
or hospital admissions, based on 10th revision of the
International Statistical Classification of Diseases and Related Health
Problems (code: L29). To reduce
heterogeneity, the MR analysis was restricted to individuals whose
ethnic backgrounds were White (including British, Irish, and other White
backgrounds), with genetic information available.