Interactions between adiposity and genetic polymorphisms on the risk of psoriasis.
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.


OBJECTIVE
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 (P ) < 0·05], but not for rs7530511. These observations were confirmed among participants without type 2 diabetes 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 rs7530511.


CONCLUSIONS
The association between a polymorphism in IL12B and psoriasis risk may be modified by measures of overall and central adiposity.
Department of Dermatology, Harvard Medical School, Brigham and Women's Hospital, 41 Ave. Louis Pasteur, Boston, MA 02115, USA.
W-Q
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Li
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JL
Han
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MF
Zhang
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Qureshi
D050154:Adiposity / Q000235:genetics*; D015992:Body Mass Index; D005260:Female; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011565:Psoriasis / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics; D012307:Risk Factors; D049629:Waist-Hip Ratio
C500879:IL12B protein, human; C515500:IL23R protein, human; D053762:Interleukin-12 Subunit p40; D018123:Receptors, Interleukin