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Genome-wide association scan yields new insights into the immunopathogenesis of psoriasis

Genes & Immunity volume 10, pages 201–209 (2009)Cite this article

Abstract

Psoriasis is a common, immunologically mediated, inflammatory and hyperproliferative disease of the skin and joints, with a multifactorial genetic basis. We earlier mapped PSORS1, the major psoriasis susceptibility gene in the major histocompatibility complex (MHC), to within or very near HLA-Cw6. In an effort to identify non-MHC psoriasis genes, we carried out a collaborative genome-wide association study. After the initial follow-up genotyping of 21 single nucleotide polymorphisms from 18 loci, showing strong evidence of association in the initial scan, we confirmed evidence of association at seven loci. Three of these loci confirm earlier reports of association (HLA-C, IL12B, IL23R) and four identify novel signals located near plausible candidate genes (IL23A, IL4/IL13, TNFAIP3 and TNIP1). In other work, we have also shown that interferon-γ (IFN-γ) treatment induces interleukin (IL)-23 mRNA and protein in antigen-presenting cells (APC), leading to the proliferation of CD4+ and CD8+ memory T cells expressing IL-17. Although functional variants remain to be identified, we speculate that genetic variants at the IL4/IL13 locus contribute to the Th1 bias that is characteristic of psoriasis, that Th1-derived IFN-γ supports expansion of IL-17+ T cells through APC-derived IL-23 and that negative regulation of inflammatory signaling through the NF-κB axis is impaired because of genetic variants of TNFAIP3 and TNIP1.

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References

  1. Sander HM, Morris LF, Phillips CM, Harrison PE, Menter A . The annual cost of psoriasis. J Am Acad Dermatol 1993; 28: 422–425.

    Article  CAS  PubMed  Google Scholar 

  2. Gupta MA, Schork NJ, Gupta AK, Kirkby S, Ellis CN . Suicidal ideation in psoriasis. Int J Dermatol 1993; 32: 188–190.

    Article  CAS  PubMed  Google Scholar 

  3. Krueger GG, Bergstresser PR, Lowe NJ, Voorhees JJ, Weinstein GD . Psoriasis. J Am Acad Dermatol 1984; 11 (5 Pt 2): 937–947.

    Article  CAS  PubMed  Google Scholar 

  4. Gladman DD . Natural history of psoriatic arthritis. Baillieres Clin Rheumatol 1994; 8: 379–394.

    Article  CAS  PubMed  Google Scholar 

  5. Gudjonsson JE, Elder JT . Psoriasis. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AM, Leffell DJ (eds). Fitzpatrick′s Dermatology in General Medicine, vol. 1 McGraw-Hill: New York, 2007, pp 169–194.

    Google Scholar 

  6. Gudjonsson JE, Elder JT . Psoriasis: epidemiology. Clin Dermatol 2007; 25: 535–546.

    Article  PubMed  Google Scholar 

  7. Elder JT, Nair RP, Guo SW, Henseler T, Christophers E, Voorhees JJ . The genetics of psoriasis. Arch Dermatol 1994; 130: 216–224.

    Article  CAS  PubMed  Google Scholar 

  8. Elder JT, Nair RP, Henseler T, Jenisch S, Stuart P, Chia N et al. The genetics of psoriasis 2001: the odyssey continues. Arch Dermatol 2001; 137: 1447–1454.

    Article  CAS  PubMed  Google Scholar 

  9. Henseler T, Christophers E . Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris. J Am Acad Dermatol 1985; 13: 450–456.

    Article  CAS  PubMed  Google Scholar 

  10. Moll JM, Wright V, O'Neill T, Silman AJ . Familial occurrence of psoriatic arthritis. Ann Rheum Dis 1973; 32: 181–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chandran V, Pellett FJ, Shanmugarajah S, Schentag CT, Brockbank J, Toloza S et al. Recurrence risk of psoriatic arthritis (PsA) and psoriasis (Ps) in relatives of patients with PsA (abstract). Arthritis Rheum 2007; 56 (Suppl 9): S798.

    Google Scholar 

  12. Mallon E, Bunce M, Savoie H, Rowe A, Newson R, Gotch F et al. HLA-C and guttate psoriasis. Br J Dermatol 2000; 143: 1177–1182.

    Article  CAS  PubMed  Google Scholar 

  13. Ozawa A, Miyahara M, Sugai J, Iizuka M, Kawakubo Y, Matsuo I et al. HLA class I and II alleles and susceptibility to generalized pustular psoriasis: significant associations with HLA-Cw1 and HLA-DQB1*0303. J Dermatol 1998; 25: 573–581.

    Article  CAS  PubMed  Google Scholar 

  14. Torii H, Nakagawa H, Ishibashi Y, Tokunaga K, Juji T . Genetic polymorphisms in HLA-A, -B, -C and -DR antigens in Japanese patients with palmoplantar pustulosis. Dermatology 1994; 188: 290–292.

    Article  CAS  PubMed  Google Scholar 

  15. Lowes MA, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba LC, Haider AS et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17T cells. J Invest Dermatol 2008; 128: 1207–1211.

    Article  CAS  PubMed  Google Scholar 

  16. Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M et al. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 2007; 13: 1173–1175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Neurath MF . IL-23: a master regulator in Crohn disease. Nat Med 2007; 13: 26–28.

    Article  CAS  PubMed  Google Scholar 

  18. Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J et al. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 2007; 445: 648–651.

    Article  CAS  PubMed  Google Scholar 

  19. Ma HL, Liang S, Li J, Napierata L, Brown T, Benoit S et al. IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest 2008; 118: 597–607.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 2007; 8: 950–957.

    Article  CAS  PubMed  Google Scholar 

  21. Sa SM, Valdez PA, Wu J, Jung K, Zhong F, Hall L et al. The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. J Immunol 2007; 178: 2229–2240.

    Article  CAS  PubMed  Google Scholar 

  22. Wolk K, Witte E, Wallace E, Docke WD, Kunz S, Asadullah K et al. IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 2006; 36: 1309–1323.

    Article  CAS  PubMed  Google Scholar 

  23. Wolk K, Kunz S, Asadullah K, Sabat R . Cutting edge: immune cells as sources and targets of the IL-10 family members? J Immunol 2002; 168: 5397–5402.

    Article  CAS  PubMed  Google Scholar 

  24. Kryczek I, Bruce AT, Gudjonsson JE, Johnston A, Vatan L, Szeliga W et al. Induction of memory IL-17+ T cell trafficking and expansion by IFN-gamma: mechanism and pathological relevance. J Immunol 2008; 181: 4733–4741.

    Article  CAS  PubMed  Google Scholar 

  25. Conrad C, Boyman O, Tonel G, Tun-Kyi A, Laggner U, de Fougerolles A et al. Alpha1beta1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis. Nat Med 2007; 13: 836–842.

    Article  CAS  PubMed  Google Scholar 

  26. Altshuler D, Brooks LD, Chakravarti A, Collins FS, Daly MJ, Donnelly P . A haplotype map of the human genome. Nature 2005; 437: 1299–1320.

    Article  CAS  Google Scholar 

  27. Manolio TA, Rodriguez LL, Brooks L, Abecasis G, Ballinger D, Daly M et al. New models of collaboration in genome-wide association studies: the Genetic Association Information Network. Nat Genet 2007; 39: 1045–1051.

    Article  CAS  PubMed  Google Scholar 

  28. Nair RP, Callis Duffin K, Helms C, Ding J, Stuart PE, Goldgar D et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kB pathways. Nat Genet 2009; 41: 199–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nair RP, Stuart PE, Nistor I, Hiremagalore R, Chia NV, Jenisch S et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet 2006; 78: 827–851.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gudjonsson JE, Karason A, Runarsdottir EH, Antonsdottir AA, Hauksson VB, Jonsson HH et al. Distinct clinical differences between HLA-Cw*0602 positive and negative psoriasis patients--an analysis of 1019 HLA-C- and HLA-B-typed patients. J Invest Dermatol 2006; 126: 740–745.

    Article  CAS  PubMed  Google Scholar 

  31. Tsunemi Y, Saeki H, Nakamura K, Sekiya T, Hirai K, Fujita H et al. Interleukin-12 p40 gene (IL12B) 3′-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris. J Dermatol Sci 2002; 30: 161–166.

    Article  CAS  PubMed  Google Scholar 

  32. Capon F, Di Meglio P, Szaub J, Prescott NJ, Dunster C, Baumber L et al. Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis. Hum Genet 2007; 122: 201–206.

    Article  CAS  PubMed  Google Scholar 

  33. Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 2007; 80: 273–290.

    Article  CAS  PubMed  Google Scholar 

  34. Akagi Y, Kimura T, Kunimoto M, Kuki K, Tabata T . A role of tonsillar lymphocyte for focal infection. With special reference to lymphocyte adhesion to vessels in dermis. Adv Otorhinolaryngol 1992; 47: 129–133.

    CAS  PubMed  Google Scholar 

  35. Diluvio L, Vollmer S, Besgen P, Ellwart JW, Chimenti S, Prinz JC . Identical TCR beta-chain rearrangements in streptococcal angina and skin lesions of patients with psoriasis vulgaris. J Immunol 2006; 176: 7104–7111.

    Article  CAS  PubMed  Google Scholar 

  36. Chang JC, Smith LR, Froning KJ, Schwabe BJ, Laxer JA, Caralli LL et al. CD8+ T cells in psoriatic lesions preferentially use T-cell receptor V beta 3 and/or V beta 13.1 genes. Proc Natl Acad Sci USA 1994; 91: 9282–9286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Prinz JC, Vollmer S, Boehncke WH, Menssen A, Laisney I, Trommler P . Selection of conserved TCR VDJ rearrangements in chronic psoriatic plaques indicates a common antigen in psoriasis vulgaris. Eur J Immunol 1999; 29: 3360–3368.

    Article  CAS  PubMed  Google Scholar 

  38. Vollmer S, Menssen A, Prinz JC . Dominant lesional T cell receptor rearrangements persist in relapsing psoriasis but are absent from nonlesional skin: evidence for a stable antigen-specific pathogenic T cell response in psoriasis vulgaris. J Invest Dermatol 2001; 117: 1296–1301.

    Article  CAS  PubMed  Google Scholar 

  39. Lin WJ, Norris DA, Achziger M, Kotzin BL, Tomkinson B . Oligoclonal expansion of intraepidermal T cells in psoriasis skin lesions. J Invest Dermatol 2001; 117: 1546–1553.

    Article  CAS  PubMed  Google Scholar 

  40. Jones DA, Yawalkar N, Suh KY, Sadat S, Rich B, Kupper TS . Identification of autoantigens in psoriatic plaques using expression cloning. J Invest Dermatol 2004; 123: 93–100.

    Article  CAS  PubMed  Google Scholar 

  41. Johnston A, Gudjonsson JE, Sigmundsdottir H, Love TJ, Valdimarsson H . Peripheral blood T cell responses to keratin peptides that share sequences with streptococcal M proteins are largely restricted to skin-homing CD8(+) T cells. Clin Exp Immunol 2004; 138: 83–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Baker BS, Laman JD, Powles A, van der Fits L, Voerman JS, Melief MJ et al. Peptidoglycan and peptidoglycan-specific Th1 cells in psoriatic skin lesions. J Pathol 2006; 209: 174–181.

    Article  CAS  PubMed  Google Scholar 

  43. Baker BS, Powles A, Fry L . Peptidoglycan: a major aetiological factor for psoriasis? Trends Immunol 2006; 27: 545–551.

    Article  CAS  PubMed  Google Scholar 

  44. Williams F, Meenagh A, Sleator C, Cook D, Fernandez-Vina M, Bowcock AM et al. Activating killer cell immunoglobulin-like receptor gene KIR2DS1 is associated with psoriatic arthritis. Hum Immunol 2005; 66: 836–841.

    Article  CAS  PubMed  Google Scholar 

  45. Nelson GW, Martin MP, Gladman D, Wade J, Trowsdale J, Carrington M . Cutting edge: heterozygote advantage in autoimmune disease: hierarchy of protection/susceptibility conferred by HLA and killer Ig-like receptor combinations in psoriatic arthritis. J Immunol 2004; 173: 4273–4276.

    Article  CAS  PubMed  Google Scholar 

  46. Long EO, Rajagopalan S . HLA class I recognition by killer cell Ig-like receptors. Semin Immunol 2000; 12: 101–108.

    Article  CAS  PubMed  Google Scholar 

  47. Lee E, Trepicchio WL, Oestreicher JL, Pittman D, Wang F, Chamian F et al. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med 2004; 199: 125–130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Bettelli E, Oukka M, Kuchroo VK . T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol 2007; 8: 345–350.

    Article  CAS  PubMed  Google Scholar 

  49. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006; 314: 1461–1463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Najarian DJ, Gottlieb AB . Connections between psoriasis and Crohn's disease. J Am Acad Dermatol 2003; 48: 805–821; quiz 822-804.

    Article  PubMed  Google Scholar 

  51. Mauro C, Pacifico F, Lavorgna A, Mellone S, Iannetti A, Acquaviva R et al. ABIN-1 binds to NEMO/IKKgamma and co-operates with A20 in inhibiting NF-kappaB. J Biol Chem 2006; 281: 18482–18488.

    Article  CAS  PubMed  Google Scholar 

  52. Chan JR, Blumenschein W, Murphy E, Diveu C, Wiekowski M, Abbondanzo S et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. J Exp Med 2006; 203: 2577–2587.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wang H, Kess D, Lindqvist AK, Peters T, Sindrilaru A, Wlaschek M et al. A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model. J Immunol 2008; 180: 5520–5529.

    Article  CAS  PubMed  Google Scholar 

  54. Idel S, Dansky HM, Breslow JL . A20, a regulator of NFkappaB, maps to an atherosclerosis locus and differs between parental sensitive C57BL/6J and resistant FVB/N strains. Proc Natl Acad Sci USA 2003; 100: 14235–14240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB . Risk of myocardial infarction in patients with psoriasis. JAMA 2006; 296: 1735–1741.

    Article  CAS  PubMed  Google Scholar 

  56. Graham RR, Cotsapas C, Davies L, Hackett R, Lessard CJ, Leon JM et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet 2008; 40: 1059–1061.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Musone SL, Taylor KE, Lu TT, Nititham J, Ferreira RC, Ortmann W et al. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet 2008; 40: 1062–1064.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Plenge RM, Cotsapas C, Davies L, Price AL, de Bakker PI, Maller J et al. Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet 2007; 39: 1477–1482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Thomson W, Barton A, Ke X, Eyre S, Hinks A, Bowes J et al. Rheumatoid arthritis association at 6q23. Nat Genet 2007; 39: 1431–1433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Griffiths CE, Barker JN . Pathogenesis and clinical features of psoriasis. Lancet 2007; 370: 263–271.

    Article  CAS  PubMed  Google Scholar 

  61. Ghoreschi K, Thomas P, Breit S, Dugas M, Mailhammer R, van Eden W et al. Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease. Nat Med 2003; 9: 40–46.

    Article  CAS  PubMed  Google Scholar 

  62. Lee GR, Fields PE, Griffin TJ, Flavell RA . Regulation of the Th2 cytokine locus by a locus control region. Immunity 2003; 19: 145–153.

    Article  CAS  PubMed  Google Scholar 

  63. Brody I . Alterations of clinically normal skin in early eruptive guttate psoriasis. J Cutan Pathol 1978; 5: 219–233.

    Article  CAS  PubMed  Google Scholar 

  64. Ragaz A, Ackerman AB . Evolution, maturation, and regression of lesions of psoriasis. New observations and correlation of clinical and histologic findings. Am J Dermatopathol 1979; 1: 199–214.

    Article  CAS  PubMed  Google Scholar 

  65. Schubert C, Christophers E . Mast cells and macrophages in early relapsing psoriasis. Arch Dermatol Res 1985; 277: 352–358.

    Article  CAS  PubMed  Google Scholar 

  66. Braun-Falco O, Schmoeckel C . The dermal inflammatory reaction in initial psoriatic lesions. Arch Dermatol Res 1977; 258: 9–16.

    Article  CAS  PubMed  Google Scholar 

  67. Wollenberg A, Wagner M, Gunther S, Towarowski A, Tuma E, Moderer M et al. Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. J Invest Dermatol 2002; 119: 1096–1102.

    Article  CAS  PubMed  Google Scholar 

  68. Nestle FO, Conrad C, Tun-Kyi A, Homey B, Gombert M, Boyman O et al. Plasmacytoid predendritic cells initiate psoriasis through interferon-{alpha} production. J Exp Med 2005; 202: 135–143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Braun-Falco O . Dynamics of growth and regression in psoriatic lesions: alterations in the skin from normal into a psoriatic lesion, and during regression of psoriatic lesions. In: Farber EM, Cox AJ (eds). Psoriasis: Proceedings of the International Symposium, Stanford University, 1971. Stanford University Press: Stanford, CA, 1971, pp 215–237.

    Google Scholar 

  70. Boehncke WH, Wortmann S, Kaufmann R, Mielke V, Sterry W . A subset of macrophages located along the basement membrane (‘lining cells’) is a characteristic histopathological feature of psoriasis. Am J Dermatopathol 1995; 17: 139–144.

    Article  CAS  PubMed  Google Scholar 

  71. van den Oord JJ, de Wolf-Peeters C . Epithelium-lining macrophages in psoriasis. Br J Dermatol 1994; 130: 589–594.

    Article  CAS  PubMed  Google Scholar 

  72. Bata-Csorgo Z, Cooper KD, Ting KM, Voorhees JJ, Hammerberg C . Fibronectin and alpha5 integrin regulate keratinocyte cell cycling. A mechanism for increased fibronectin potentiation of T cell lymphokine-driven keratinocyte hyperproliferation in psoriasis. J Clin Invest 1998; 101: 1509–1518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Brody I . Mast cell degranulation in the evolution of acute eruptive guttate psoriasis vulgaris. J Invest Dermatol 1984; 82: 460–464.

    Article  CAS  PubMed  Google Scholar 

  74. Stoler A, Kopan R, Duvic M, Fuchs E . Use of monospecific antisera and cRNA probes to localize the major changes in keratin expression during normal and abnormal epidermal differentiation. J Cell Biol 1988; 107: 427–446.

    Article  CAS  PubMed  Google Scholar 

  75. Leigh IM, Navsaria H, Purkis PE, McKay IA, Bowden PE, Riddle PN . Keratins (K16 and K17) as markers of keratinocyte hyperproliferation in psoriasis in vivo and in vitro. Br J Dermatol 1995; 133: 501–511.

    Article  CAS  PubMed  Google Scholar 

  76. Zhou X, Krueger JG, Kao MC, Lee E, Du F, Menter A et al. Novel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63 100-element oligonucleotide array. Physiol Genomics 2003; 13: 69–78.

    Article  CAS  PubMed  Google Scholar 

  77. Gudjonsson JE, Ding J, Li X, Nair RP, Stuart PE, Tejasvi T et al. Global gene expression analysis reveals evidence for decreased lipid biosynthesis and increased innate immunity in uninvolved psoriatic skin. J Invest Dermatol 2009 (submitted).

  78. Capon F, Novelli G, Semprini S, Clementi M, Nudo M, Vultaggio P et al. Searching for psoriasis susceptibility genes in Italy: genome scan and evidence for a new locus on chromosome 1. J Invest Dermatol 1999; 112: 32–35.

    Article  CAS  PubMed  Google Scholar 

  79. Capon F, Semprini S, Chimenti S, Fabrizi G, Zambruno G, Murgia S et al. Fine mapping of the PSORS4 psoriasis susceptibility region on chromosome 1q21. J Invest Dermatol 2001; 116: 728–730.

    Article  CAS  PubMed  Google Scholar 

  80. Bowcock AM . Genetic association in psoriasis. In: Eighth International Psoriasis Genetics Committee Meeting Paris, France 2005, (unpublished).

  81. Bhalerao J, Bowcock AM . The genetics of psoriasis: a complex disorder of the skin and immune system. Hum Mol Genet 1998; 7: 1537–1545.

    Article  CAS  PubMed  Google Scholar 

  82. de Cid R, Riveira-Munoz E, Zeeuwen PLJM, Robarge J, Liao W, Dannhauser E et al. Deletion of the late cornified envelope (LCE) 3C and 3B genes as a susceptibility factor for psoriasis. Nat Genet 2009; 41: 211–215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Hollox EJ, Huffmeier U, Zeeuwen PL, Palla R, Lascorz J, Rodijk-Olthuis D et al. Psoriasis is associated with increased beta-defensin genomic copy number. Nat Genet 2008; 40: 23–25.

    Article  CAS  PubMed  Google Scholar 

  84. Rottman JB, Smith TL, Ganley KG, Kikuchi T, Krueger JG . Potential role of the chemokine receptors CXCR3, CCR4, and the integrin alphaEbeta7 in the pathogenesis of psoriasis vulgaris. Lab Invest 2001; 81: 335–347.

    Article  CAS  PubMed  Google Scholar 

  85. Stratis A, Pasparakis M, Rupec RA, Markur D, Hartmann K, Scharffetter-Kochanek K et al. Pathogenic role for skin macrophages in a mouse model of keratinocyte-induced psoriasis-like skin inflammation. J Clin Invest 2006; 116: 2094–2104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Wang H, Peters T, Kess D, Sindrilaru A, Oreshkova T, Van Rooijen N et al. Activated macrophages are essential in a murine model for T cell-mediated chronic psoriasiform skin inflammation. J Clin Invest 2006; 116: 2105–2114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Bata-Csorgo Z, Hammerberg C, Voorhees JJ, Cooper KD . Kinetics and regulation of human keratinocyte stem cell growth in short-term primary ex vivo culture. Cooperative growth factors from psoriatic lesional T lymphocytes stimulate proliferation among psoriatic uninvolved, but not normal, stem keratinocytes. J Clin Invest 1995; 95: 317–327.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Iordanov MS, Sundholm AJ, Simpson EL, Hanifin JM, Ryabinina OP, Choi RJ et al. Cell death-induced activation of epidermal growth factor receptor in keratinocytes: implications for restricting epidermal damage in dermatitis. J Invest Dermatol 2005; 125: 134–142.

    Article  CAS  PubMed  Google Scholar 

  89. Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 2007; 316: 1331–1336.

    Article  CAS  PubMed  Google Scholar 

  90. Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 2008; 40: 161–169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet 2008; 40: 189–197.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Weedon MN, Lettre G, Freathy RM, Lindgren CM, Voight BF, Perry JR et al. A common variant of HMGA2 is associated with adult and childhood height in the general population. Nat Genet 2007; 39: 1245–1250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Sanna S, Jackson AU, Nagaraja R, Willer CJ, Chen WM, Bonnycastle LL et al. Common variants in the GDF5-UQCC region are associated with variation in human height. Nat Genet 2008; 40: 198–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Weedon MN, Lango H, Lindgren CM, Wallace C, Evans DM, Mangino M et al. Genome-wide association analysis identifies 20 loci that influence adult height. Nat Genet 2008; 40: 575–583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet 2008; 40: 955–962.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Chaudhari U, Romano P, Mulcahy LD, Dooley LT, Baker DG, Gottlieb AB . Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial. Lancet 2001; 357: 1842–1847.

    Article  CAS  PubMed  Google Scholar 

  97. Krueger GG, Langley RG, Leonardi C, Yeilding N, Guzzo C, Wang Y et al. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med 2007; 356: 580–592.

    Article  CAS  PubMed  Google Scholar 

  98. Nair RP, Ruether A, Stuart PE, Jenisch S, Tejasvi T, Hiremagalore R et al. Polymorphisms of the IL12B and IL23R genes are associated with psoriasis. J Invest Dermatol 2008; 128: 1653–1661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA

    J T Elder

  2. Department of Dermatology, Ann Arbor VA Health System, Ann Arbor, MI, USA

    J T Elder

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Elder, J. Genome-wide association scan yields new insights into the immunopathogenesis of psoriasis. Genes Immun 10, 201–209 (2009). https://doi.org/10.1038/gene.2009.11

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