Background: Adiposity is a known risk factor for psoriasis. Genome-wide association studies (GWAS) have identified a number of genes associated with risk of psoriasis while the evidence on gene-environment interactions in psoriasis is very sparse. Objectives: To investigate the effect modification by adiposity measures on the association between single-nucleotide polymorphisms (SNPs) from published GWAS and risk of psoriasis. Methods: Our psoriasis GWAS dataset comprised 9194 participants, including 337 individuals with psoriasis and 8857 controls from six GWAS, nested within the Nurses' Health Study (NHS), NHS II, and Health Professionals' Follow-up Study. Clinician-diagnosed psoriasis was ascertained with high validity. For stratified analyses, body mass index (BMI) was dichotomized at 25, and waist circumference was dichotomized at 30 (women) and 36 inches (men), while waist-hip ratio (WHR) was dichotomized at 0.8 (women) and 1.0 (men). Results: Forty-one out of 44 previously reported psoriasis-related SNPs were included in our GWAS datasets. After excluding those with high linkage disequilibrium, 33 remained in the analysis. There were significant interactions between BMI and two SNPs in the IL12B (rs3212227) and IL23R (rs7530511) genes. Further analysis of these two SNPs indicated interactions between rs3212227 and waist circumference or WHR [P for interaction (Pint) < 0.05], but not for rs7530511. These observations were confirmed among participants without type 2diabetes or coronary heart disease. The interactions remained after simultaneously adjusting for BMI as a continuous variable. In addition, we did not observe a significant main effect for rs 7530511. Conclusions: The association between a polymorphism in IL12B and psoriasis risk may be modified by measures of overall and central adiposity.
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