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Detailed genetic characterization of the interleukin-23 receptor in psoriasis

Genes & Immunity volume 9, pages 546–555 (2008)Cite this article

Abstract

Using a multi-tiered, case–control association design, scanning 25 215 gene-centric SNPs, we previously identified two psoriasis susceptibility genes: IL12B and IL23R. These results have recently been confirmed. To better characterize the IL23R psoriasis-association, we used a fine mapping strategy to identify 59 additional IL23R-linked SNPs, which were genotyped in our three independent, white North American sample sets (>2800 individuals in toto). A sliding window of haplotype association demonstrates colocalization of psoriasis susceptibility effects within the boundaries of IL23R across all sample sets, thereby decreasing the likelihood that neighboring genes, particularly IL12RB2, are driving the association at this region. Additional haplotype work identified two 5-SNP haplotypes with strong protective effects, consistent across our three sample sets (ORcommon=0.67; Pcomb=4.32E-07). Importantly, heterogeneity of effect was extremely low between sample sets for these haplotypes (PHet=0.961). Together, these protective haplotypes attain a frequency of 16% in controls, declining to 11% in cases. The characterization of association patterns within IL23R to specific predisposing/protective variants will play an important role in the elucidation of psoriasis etiology and other related phenotypes. Further, this work is essential to lay the foundation for the role of IL23R genetics in response to pharmaceutical therapy and dosage.

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Acknowledgements

We are grateful to all the individuals with psoriasis and control subjects for participation in this study. We thank J Sninsky and T White for their comments on the paper, scientific advice and support. We also thank the members of the Celera High Throughput Lab and Computational Biology Group, S Prescott, M Paul, A Lindell, everyone at Lineagen, E Beasley, L McAllister and M Cargill for key help with this project. This study was supported in part by a Public Health Services research grant to the Huntsman General Clinical Research Center at the University of Utah, by National Center for Research Resources Grant M01-RR00064 and by generous gifts from the WM Keck Foundation and from the George S and Delores Dore Eccles Foundation. Finally, we note that as current employees of Celera, VE Garcia, M Chang, N Bui, JJ Catanese, Y Li, R Brandon, AB Begovich and SJ Schrodi may hold stock or stock options in Celera.

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Authors and Affiliations

  1. Celera, 1401 Harbor Bay Parkway, Alameda, CA, USA

    V E Garcia, M Chang, R Brandon, Y Li, D Civello, C M Rowland, N Bui, J J Catanese, A B Begovich & S J Schrodi

  2. Department of Human Genetics, University of Utah, Salt Lake City, UT, USA

    N Matsunami & M F Leppert

  3. LineaGen Research Corporation, Salt Lake City, UT, USA

    N Matsunami & G G Krueger

  4. Department of Dermatology University of Utah, Salt Lake City, UT, USA

    K P Callis-Duffin, G G Krueger & M F Leppert

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  1. V E Garcia
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Correspondence to S J Schrodi.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Garcia, V., Chang, M., Brandon, R. et al. Detailed genetic characterization of the interleukin-23 receptor in psoriasis. Genes Immun 9, 546–555 (2008). https://doi.org/10.1038/gene.2008.55

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