Background: Psoriasis is an immune-mediated skin disorder that is inherited as a multifactorial trait. Linkage analyses have clearly mapped a primary disease susceptibility locus to the major histocompatibility complex (MHC) region on chromosome 6p21. More recently, whole-genome association studies have identified two non-MHC disease genes (IL12B and IL23R), both of which also confer susceptibility to Crohn disease (CD).
Objective and methods: To ascertain the genetic overlap between these two inflammatory conditions further, we investigated 15 CD-associated loci in a psoriasis case–control dataset.
Results: The analysis of 1256 patients and 2938 unrelated controls found significant associations for loci mapping to chromosomes 1q24 (rs12035082, p = 0.009), 6p22 (rs6908425, p = 0.00015) and 21q22 (rs2836754, p = 0.0003). Notably, the marker showing the strongest phenotypic effect (rs6908425) maps to CDKAL1, a gene also associated with type 2 diabetes.
Conclusions: These results substantiate emerging evidence for a pleiotropic role for s genes that contribute to the pathogenesis of immune-mediated disorders.
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Funding: The work was supported by a Medical Research Council PhD studentship (NW), a Stiefel Laboratories PhD studentship (RS), a Psoriasis Association PhD studentship (MO) and grants from the Medical Research Council (grant G0601387; RCT, JNB), The Psoriasis Association (JNB, DB, CEMG) and Arthritis Research Campaign (JW). We acknowledge use of genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council (grant G0000934) and The Wellcome Trust (grant 068545/Z/02). None of the above sponsors had any involvement in study design and execution, in the writing of the report, or in the decision to submit the paper for publication.
Competing interests: None.
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