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Insights into the pathogenesis of psoriatic arthritis from genetic studies

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Abstract

Psoriatic arthritis (PsA) is a relatively common inflammatory arthritis, a spondyloarthritis (SpA), that occurs most often in patients with psoriasis, a common immune-mediated inflammatory skin disease. Both psoriasis and PsA are highly heritable. Genetic and recent genomic studies have identified variants associated with psoriasis and PsA, but variants differentiating psoriasis from PsA are few. In this review, we describe recent developments in understanding the genetic burden of PsA, linkage, association and epigenetic studies. Using pathway analysis, we provide further insights into the similarities and differences between PsA and psoriasis, as well as between PsA and other immune-mediated inflammatory diseases, particularly ankylosing spondylitis, another SpA. Environmental factors that may trigger PsA in patients with psoriasis are also reviewed. To further understand the pathogenetic differences between PsA and psoriasis as well as other SpA, larger cohort studies of well-phenotyped subjects with integrated analysis of genomic, epigenomic, transcriptomic, proteomic and metabolomic data using interomic system biology approaches are required.

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References

  1. Zeidler H, Amor B (2011) The Assessment in Spondyloarthritis International Society (ASAS) classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general: the spondyloarthritis concept in progress. Ann Rheum Dis 70:1–3. https://doi.org/10.1136/ard.2010.135889

    Article  PubMed  Google Scholar 

  2. Ritchlin CT, Colbert RA, Gladman DD (2017) Psoriatic arthritis. N Engl J Med 376:957–970. https://doi.org/10.1056/NEJMra1505557

    Article  PubMed  Google Scholar 

  3. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H, CASPAR Study Group (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54:2665–2673. https://doi.org/10.1002/art.21972

    Article  PubMed  Google Scholar 

  4. McHugh N, Maguire Á, Handel I, Tillett W, Morris J, Hawkins N, Cavill C, Korendowych E, Mughal F (2020) Evaluation of the economic burden of psoriatic arthritis and the relationship between functional status and healthcare costs. J Rheumatol 47:701–707. https://doi.org/10.3899/jrheum.190083

    Article  PubMed  Google Scholar 

  5. Scotti L, Franchi M, Marchesoni A, Corrao G (2018) Prevalence and incidence of psoriatic arthritis: a systematic review and meta-analysis. Semin Arthritis Rheum 48:28–34. https://doi.org/10.1016/j.semarthrit.2018.01.003

    Article  PubMed  Google Scholar 

  6. Alinaghi F, Calov M, Kristensen LE, Gladman DD, Coates LC, Jullien D, Gottlieb AB, Gisondi P, Wu JJ, Thyssen JP, Egeberg A (2019) Prevalence of psoriatic arthritis in patients with psoriasis: a systematic review and meta-analysis of observational and clinical studies. J Am Acad Dermatol 80:251–265.e19. https://doi.org/10.1016/j.jaad.2018.06.027

    Article  PubMed  Google Scholar 

  7. Burton PR, Tobin MD, Hopper JL (2005) Key concepts in genetic epidemiology. Lancet 366:941–951. https://doi.org/10.1016/S0140-6736(05)67322-9

    Article  PubMed  Google Scholar 

  8. Dougados M, Baeten D (2011) Spondyloarthritis. Lancet 377:2127–2137. https://doi.org/10.1016/S0140-6736(11)60071-8

    Article  PubMed  Google Scholar 

  9. Pittam B, Gupta S, Harrison NL, Robertson S, Hughes DM, Zhao SS (2020) Prevalence of extra-articular manifestations in psoriatic arthritis: a systematic review and meta-analysis. Rheumatology (Oxford) 59:2199–2206. https://doi.org/10.1093/rheumatology/keaa062

    Article  Google Scholar 

  10. Rida MA, Chandran V (2020) Challenges in the clinical diagnosis of psoriatic arthritis. Clin Immunol 214:108390. https://doi.org/10.1016/j.clim.2020.108390

    Article  CAS  PubMed  Google Scholar 

  11. Olivieri I, Padula A, D’Angelo S, Cutro MS (2009) Psoriatic arthritis sine psoriasis. J Rheumatol Suppl 83:28–29. https://doi.org/10.3899/jrheum.090218

    Article  PubMed  Google Scholar 

  12. Chandran V, Schentag CT, Brockbank JE, Pellett FJ, Shanmugarajah S, Toloza SM, Rahman P, Gladman DD (2009) Familial aggregation of psoriatic arthritis. Ann Rheum Dis 68:664–667. https://doi.org/10.1136/ard.2008.089367

    Article  CAS  PubMed  Google Scholar 

  13. Moll JM, Wright V (1973) Familial occurrence of psoriatic arthritis. Ann Rheum Dis 32:181–201. https://doi.org/10.1136/ard.32.3.181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Karason A, Love TJ, Gudbjornsson B (2009) A strong heritability of psoriatic arthritis over four generations--the Reykjavik Psoriatic Arthritis Study. Rheumatology (Oxford) 48:1424–1428. https://doi.org/10.1093/rheumatology/kep243

    Article  Google Scholar 

  15. Yang J, Zeng J, Goddard ME, Wray NR, Visscher PM (2017) Concepts, estimation and interpretation of SNP-based heritability. Nat Genet 49:1304–1310. https://doi.org/10.1038/ng.3941

    Article  CAS  PubMed  Google Scholar 

  16. Li Q, Chandran V, Tsoi L, O’Rielly D, Nair RP, Gladman D, Elder JT, Rahman P (2020) Quantifying differences in heritability among psoriatic arthritis (PsA), cutaneous psoriasis (PsC) and psoriasis vulgaris (PsV). Sci Rep 10:4925. https://doi.org/10.1038/s41598-020-61981-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273:1516–1517. https://doi.org/10.1126/science.273.5281.1516

    Article  CAS  PubMed  Google Scholar 

  18. Capon F (2017) The genetic basis of psoriasis. Int J Mol Sci 18:2526. https://doi.org/10.3390/ijms18122526

    Article  CAS  PubMed Central  Google Scholar 

  19. FitzGerald O, Haroon M, Giles JT, Winchester R (2015) Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype. Arthritis Res Ther 17:115. https://doi.org/10.1186/s13075-015-0640-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Stuart PE, Tsoi LC, Hambro CA, Elder JT (2018) Genetics of psoriasis. In: Fitzgerald O, Gladman D (eds) Oxford textbook of psoriatic arthritis, 1st edn. Oxford University Press, Oxford, pp 35–55

    Google Scholar 

  21. Rahmati S, Tsoi L, O’Rielly D, Chandran V, Rahman P (2020) Complexities in genetics of psoriatic arthritis. Curr Rheumatol Rep 22:10. https://doi.org/10.1007/s11926-020-0886-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shi C, Rattray M, Barton A, Bowes J, Orozco G (2020) Using functional genomics to advance the understanding of psoriatic arthritis. Rheumatology (Oxford) 59:3137–3146. https://doi.org/10.1093/rheumatology/keaa283

    Article  Google Scholar 

  23. Stuart PE, Nair RP, Tsoi LC, Tejasvi T, Das S, Kang HM, Ellinghaus E, Chandran V, Callis-Duffin K, Ike R, Li Y, Wen X, Enerbäck C, Gudjonsson JE, Kõks S, Kingo K, Esko T, Mrowietz U, Reis A, Wichmann HE, Gieger C, Hoffmann P, Nöthen MM, Winkelmann J, Kunz M, Moreta EG, Mease PJ, Ritchlin CT, Bowcock AM, Krueger GG, Lim HW, Weidinger S, Weichenthal M, Voorhees JJ, Rahman P, Gregersen PK, Franke A, Gladman DD, Abecasis GR, Elder JT (2015) Genome-wide association analysis of psoriatic arthritis and cutaneous psoriasis reveals differences in their genetic architecture. Am J Hum Genet 97:816–836. https://doi.org/10.1016/j.ajhg.2015.10.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Eder L, Chandran V, Pellet F, Shanmugarajah S, Rosen CF, Bull SB, Gladman DD (2012) Human leucocyte antigen risk alleles for psoriatic arthritis among patients with psoriasis. Ann Rheum Dis 71:50–55. https://doi.org/10.1136/ard.2011.155044

    Article  PubMed  Google Scholar 

  25. Winchester R, Minevich G, Steshenko V, Kirby B, Kane D, Greenberg DA, FitzGerald O (2012) HLA associations reveal genetic heterogeneity in psoriatic arthritis and in the psoriasis phenotype. Arthritis Rheum 64:1134–1144. https://doi.org/10.1002/art.33415

    Article  CAS  PubMed  Google Scholar 

  26. Okada Y, Han B, Tsoi LC, Stuart PE, Ellinghaus E, Tejasvi T, Chandran V, Pellett F, Pollock R, Bowcock AM, Krueger GG, Weichenthal M, Voorhees JJ, Rahman P, Gregersen PK, Franke A, Nair RP, Abecasis GR, Gladman DD, Elder JT, de Bakker PI, Raychaudhuri S (2014) Fine mapping major histocompatibility complex associations in psoriasis and its clinical subtypes. Am J Hum Genet 95:162–172. https://doi.org/10.1016/j.ajhg.2014.07.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bowes J, Ashcroft J, Dand N, Jalali-Najafabadi F, Bellou E, Ho P, Marzo-Ortega H, Helliwell PS, Feletar M, Ryan AW, Kane DJ, Korendowych E, Simpson MA, Packham J, McManus R, Brown MA, Smith CH, Barker JN, McHugh N, FitzGerald O, Warren RB, Barton A (2017) Cross-phenotype association mapping of the MHC identifies genetic variants that differentiate psoriatic arthritis from psoriasis. Ann Rheum Dis 76:1774–1779. https://doi.org/10.1136/annrheumdis-2017-211414

    Article  CAS  PubMed  Google Scholar 

  28. Cortes A, Brown MA (2011) Promise and pitfalls of the Immunochip. Arthritis Res Ther 13:101. https://doi.org/10.1186/ar3204

    Article  PubMed  PubMed Central  Google Scholar 

  29. Bowes J, Budu-Aggrey A, Huffmeier U, Uebe S, Steel K, Hebert HL, Wallace C, Massey J, Bruce IN, Bluett J, Feletar M, Morgan AW, Marzo-Ortega H, Donohoe G, Morris DW, Helliwell P, Ryan AW, Kane D, Warren RB, Korendowych E, Alenius GM, Giardina E, Packham J, McManus R, FitzGerald O, McHugh N, Brown MA, Ho P, Behrens F, Burkhardt H, Reis A, Barton A (2015) Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis. Nat Commun 6:6046. https://doi.org/10.1038/ncomms7046

    Article  CAS  PubMed  Google Scholar 

  30. Aterido A, Cañete JD, Tornero J, Ferrándiz C, Pinto JA, Gratacós J, Queiró R, Montilla C, Torre-Alonso JC, Pérez-Venegas JJ, Fernández Nebro A, Muñoz-Fernández S, González CM, Roig D, Zarco P, Erra A, Rodríguez J, Castañeda S, Rubio E, Salvador G, Díaz-Torné C, Blanco R, Willisch Domínguez A, Mosquera JA, Vela P, Sánchez-Fernández SA, Corominas H, Ramírez J, de la Cueva P, Fonseca E, Fernández E, Puig L, Dauden E, Sánchez-Carazo JL, López-Estebaranz JL, Moreno D, Vanaclocha F, Herrera E, Blanco F, Fernández-Gutiérrez B, González A, Pérez-García C, Alperi-López M, Olivé Marques A, Martínez-Taboada V, González-Álvaro I, Sanmartí R, Tomás Roura C, García-Montero AC, Bonàs-Guarch S, Mercader JM, Torrents D, Codó L, Gelpí JL, López-Corbeto M, Pluma A, López-Lasanta M, Tortosa R, Palau N, Absher D, Myers R, Marsal S, Julià A (2019) Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis. Ann Rheum Dis 78:e214158. https://doi.org/10.1136/annrheumdis-2018-214158

    Article  CAS  PubMed  Google Scholar 

  31. Jordan CT, Cao L, Roberson ED, Duan S, Helms CA, Nair RP, Duffin KC, Stuart PE, Goldgar D, Hayashi G, Olfson EH, Feng BJ, Pullinger CR, Kane JP, Wise CA, Goldbach-Mansky R, Lowes MA, Peddle L, Chandran V, Liao W, Rahman P, Krueger GG, Gladman D, Elder JT, Menter A, Bowcock AM (2012) Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis. Am J Hum Genet 90:796–808. https://doi.org/10.1016/j.ajhg.2012.03.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Dand N, Mucha S, Tsoi LC, Mahil SK, Stuart PE, Arnold A, Baurecht H, Burden AD, Callis Duffin K, Chandran V, Curtis CJ, Das S, Ellinghaus D, Ellinghaus E, Enerback C, Esko T, Gladman DD, Griffiths CEM, Gudjonsson JE, Hoffman P, Homuth G, Hüffmeier U, Krueger GG, Laudes M, Lee SH, Lieb W, Lim HW, Löhr S, Mrowietz U, Müller-Nurayid M, Nöthen M, Peters A, Rahman P, Reis A, Reynolds NJ, Rodriguez E, Schmidt CO, Spain SL, Strauch K, Tejasvi T, Voorhees JJ, Warren RB, Weichenthal M, Weidinger S, Zawistowski M, Nair RP, Capon F, Smith CH, Trembath RC, Abecasis GR, Elder JT, Franke A, Simpson MA, Barker JN (2017) Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling. Hum Mol Genet 26:4301–4313. https://doi.org/10.1093/hmg/ddx328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Budu-Aggrey A, Bowes J, Stuart PE, Zawistowski M, Tsoi LC, Nair R, Jadon DR, McHugh N, Korendowych E, Elder JT, Barton A, Raychaudhuri S (2017) A rare coding allele in IFIH1 is protective for psoriatic arthritis. Ann Rheum Dis 76:1321–1324. https://doi.org/10.1136/annrheumdis-2016-210592

    Article  CAS  PubMed  Google Scholar 

  34. Julià A, Pinto JA, Gratacós J, Queiró R, Ferrándiz C, Fonseca E, Montilla C, Torre-Alonso JC, Puig L, Pérez Venegas JJ, Fernández Nebro A, Fernández E, Muñoz-Fernández S, Daudén E, González C, Roig D, Sánchez Carazo JL, Zarco P, Erra A, López Estebaranz JL, Rodríguez J, Ramírez DM, de la Cueva P, Vanaclocha F, Herrera E, Castañeda S, Rubio E, Salvador G, Díaz-Torné C, Blanco R, Willisch Domínguez A, Mosquera JA, Vela P, Tornero J, Sánchez-Fernández S, Corominas H, Ramírez J, López-Lasanta M, Tortosa R, Palau N, Alonso A, García-Montero AC, Gelpí JL, Codó L, Day K, Absher D, Myers RM, Cañete JD, Marsal S (2015) A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk. Ann Rheum Dis 74:1875–1881. https://doi.org/10.1136/annrheumdis-2014-207190

    Article  CAS  PubMed  Google Scholar 

  35. Stuart PE, Huffmeier U, Nair RP, Palla R, Tejasvi T, Schalkwijk J, Elder JT, Reis A, Armour JA (2012) Association of beta-defensin copy number and psoriasis in three cohorts of European origin. J Invest Dermatol 132:2407–2413. https://doi.org/10.1038/jid.2012.191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bowes J, Flynn E, Ho P, Aly B, Morgan AW, Marzo-Ortega H, Coates L, McManus R, Ryan AW, Kane D, Korendowych E, McHugh N, FitzGerald O, Packham J, Bruce IN, Barton A (2010) Variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis. Ann Rheum Dis 69:2199–2203

    Article  CAS  PubMed  Google Scholar 

  37. Li M, Wu Y, Chen G, Yang Y, Zhou D, Zhang Z, Zhang D, Chen Y, Lu Z, He L, Zheng J, Liu Y (2011) Deletion of the late cornified envelope genes LCE3C and LCE3B is associated with psoriasis in a Chinese population. J Invest Dermatol 131:1639–1643. https://doi.org/10.1038/jid.2011.86

    Article  CAS  PubMed  Google Scholar 

  38. Hüffmeier U, Estivill X, Riveira-Munoz E, Traupe H, Wendler J, Lohmann J, Böhm B, Burkhardt H, Reis A (2010) Deletion of LCE3C and LCE3B genes at PSORS4 does not contribute to susceptibility to psoriatic arthritis in German patients. Ann Rheum Dis 69:876–878. https://doi.org/10.1136/ard.2009.108951

    Article  CAS  PubMed  Google Scholar 

  39. Uebe S, Ehrlicher M, Ekici AB, Behrens F, Böhm B, Homuth G, Schurmann C, Völker U, Jünger M, Nauck M, Völzke H, Traupe H, Krawczak M, Burkhardt H, Reis A, Hüffmeier U (2017) Genome-wide association and targeted analysis of copy number variants with psoriatic arthritis in German patients. BMC Med Genet 18:92. https://doi.org/10.1186/s12881-017-0447-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Chandran V, Tolusso DC, Cook RJ, Gladman DD (2010) Risk factors for axial inflammatory arthritis in patients with psoriatic arthritis. J Rheumatol 37:809–815. https://doi.org/10.3899/jrheum.091059

    Article  PubMed  Google Scholar 

  41. Haroon M, Winchester R, Giles JT, Heffernan E, FitzGerald O (2016) Certain class I HLA alleles and haplotypes implicated in susceptibility play a role in determining specific features of the psoriatic arthritis phenotype. Ann Rheum Dis 75:155–162. https://doi.org/10.1136/annrheumdis-2014-205461

    Article  CAS  PubMed  Google Scholar 

  42. Polachek A, Cook R, Chandran V, Abji F, Gladman D, Eder L (2018) The association between HLA genetic susceptibility markers and sonographic enthesitis in psoriatic arthritis. Arthritis Rheum 70:756–762. https://doi.org/10.1002/art.40423

    Article  CAS  Google Scholar 

  43. Balding J, Kane D, Livingstone W, Mynett-Johnson L, Bresnihan B, Smith O, FitzGerald O (2003) Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity. Arthritis Rheum 48:1408–1413. https://doi.org/10.1002/art.10935

    Article  CAS  PubMed  Google Scholar 

  44. Rahman P, Snelgrove T, Peddle L, Siannis F, Farewell V, Schentag C, Gladman D (2008) A variant of the IL4 I50V single-nucleotide polymorphism is associated with erosive joint disease in psoriatic arthritis. Arthritis Rheum 58:2207–2208. https://doi.org/10.1002/art.23558

    Article  PubMed  Google Scholar 

  45. Jadon D, Tillett W, Wallis D, Cavill C, Bowes J, Waldron N, Dixon A, Sengupta R, Barton A, Korendowych E, McHugh NJ (2013) Exploring ankylosing spondylitis-associated ERAP1, IL23R and IL12B gene polymorphisms in subphenotypes of psoriatic arthritis. Rheumatology (Oxford) 52:261–266. https://doi.org/10.1093/rheumatology/kes254

    Article  CAS  Google Scholar 

  46. Pollock RA, Thavaneswaran A, Pellett F, Chandran V, Petronis A, Rahman P, Gladman DD (2015) Further evidence supporting a parent-of-origin effect in psoriatic disease. Arthritis Care Res 67:1586–1590. https://doi.org/10.1002/acr.22625

    Article  Google Scholar 

  47. Karason A, Gudjonsson JE, Upmanyu R, Antonsdottir AA, Hauksson VB, Runasdottir EH, Jonsson HH, Gudbjartsson DF, Frigge ML, Kong A, Stefansson K, Valdimarsson H, Gulcher JR (2003) A susceptibility gene for psoriatic arthritis maps to chromosome 16q: evidence for imprinting. Am J Hum Genet 72:125–131. https://doi.org/10.1086/345646

    Article  CAS  PubMed  Google Scholar 

  48. Pollock RA, Zaman L, Chandran V, Gladman DD (2019) Epigenome-wide analysis of sperm cells identifies IL22 as a possible germ line risk locus for psoriatic arthritis. PLoS One 14:e0212043. https://doi.org/10.1371/journal.pone.0212043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Patrick MT, Stuart PE, Raja K, Chi S, He Z, Voorhees JJ, Tejasvi T, Gudjonsson JE, Kahlenberg JM, Chandran V, Rahman P, Gladman DD, Nair RP, Elder JT, Tsoi LC (2019) Integrative approach to reveal cell type specificity and gene candidates for psoriatic arthritis outside the MHC. Front Genet 10:304. https://doi.org/10.3389/fgene.2019.00304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Colbert RA, Navid F, Gill T (2017) The role of HLA-B*27 in spondyloarthritis. Best Pract Res Clin Rheumatol 31:797–815. https://doi.org/10.1016/j.berh.2018.07.012

    Article  PubMed  Google Scholar 

  51. Coates LC, Baraliakos X, Blanco FJ, Blanco-Morales E, Braun J, Chandran V, Luiz Fernandez-Sueiro J, FitzGerald O, Gallagher P, Gladman DD, Gubar E, Korotaeva T, Loginova E, Lubrano E, Mulero J, Pinto J, Queiro R, Sanz J, Szentpetery A, Helliwell PS (2020) The phenotype of axial spondyloarthritis: is it dependent on HLA-B27 status? Arthritis Care Res. https://doi.org/10.1002/acr.24174

  52. Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2, Strange A, Capon F, Spencer CC, Knight J, Weale ME, Allen MH, Barton A, Band G, Bellenguez C, Bergboer JG, Blackwell JM, Bramon E, Bumpstead SJ, Casas JP, Cork MJ, Corvin A, Deloukas P, Dilthey A, Duncanson A, Edkins S, Estivill X, Fitzgerald O, Freeman C, Giardina E, Gray E, Hofer A, Hüffmeier U, Hunt SE, Irvine AD, Jankowski J, Kirby B, Langford C, Lascorz J, Leman J, Leslie S, Mallbris L, Markus HS, Mathew CG, McLean WH, McManus R, Mössner R, Moutsianas L, Naluai AT, Nestle FO, Novelli G, Onoufriadis A, Palmer CN, Perricone C, Pirinen M, Plomin R, Potter SC, Pujol RM, Rautanen A, Riveira-Munoz E, Ryan AW, Salmhofer W, Samuelsson L, Sawcer SJ, Schalkwijk J, Smith CH, Ståhle M, Su Z, Tazi-Ahnini R, Traupe H, Viswanathan AC, Warren RB, Weger W, Wolk K, Wood N, Worthington J, Young HS, Zeeuwen PL, Hayday A, Burden AD, Griffiths CE, Kere J, Reis A, McVean G, Evans DM, Brown MA, Barker JN, Peltonen L, Donnelly P, Trembath RC (2010) A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 42:985–990. https://doi.org/10.1038/ng.694

    Article  CAS  Google Scholar 

  53. Cortes A, Pulit SL, Leo PJ, Pointon JJ, Robinson PC, Weisman MH, Ward M, Gensler LS, Zhou X, Garchon HJ, Chiocchia G, Nossent J, Lie BA, Førre Ø, Tuomilehto J, Laiho K, Bradbury LA, Elewaut D, Burgos-Vargas R, Stebbings S, Appleton L, Farrah C, Lau J, Haroon N, Mulero J, Blanco FJ, Gonzalez-Gay MA, Lopez-Larrea C, Bowness P, Gaffney K, Gaston H, Gladman DD, Rahman P, Maksymowych WP, Crusius JB, van der Horst-Bruinsma IE, Valle-Oñate R, Romero-Sánchez C, Hansen IM, Pimentel-Santos FM, Inman RD, Martin J, Breban M, Wordsworth BP, Reveille JD, Evans DM, de Bakker PI, Brown MA (2015) Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1. Nat Commun 6:7146. https://doi.org/10.1038/ncomms8146

    Article  PubMed  Google Scholar 

  54. Popa OM, Cherciu M, Cherciu LI, Dutescu MI, Bojinca M, Bojinca V, Bara C, Popa LO (2016) ERAP1 and ERAP2 gene variations influence the risk of psoriatic arthritis in Romanian population. Arch Immunol Ther Exp 64(Suppl 1):123–129. https://doi.org/10.1007/s00005-016-0444-4

    Article  CAS  Google Scholar 

  55. Apel M, Uebe S, Bowes J, Giardina E, Korendowych E, Juneblad K, Pasutto F, Ekici AB, McManus R, Ho P, Bruce IN, Ryan AW, Behrens F, Böhm B, Traupe H, Lohmann J, Gieger C, Wichmann HE, Padyukov L, Fitzgerald O, Alenius GM, McHugh NJ, Novelli G, Burkhardt H, Barton A, Reis A, Hüffmeier U (2013) Variants in RUNX3 contribute to susceptibility to psoriatic arthritis, exhibiting further common ground with ankylosing spondylitis. Arthritis Rheum 65:1224–1231. https://doi.org/10.1002/art.37885

    Article  CAS  PubMed  Google Scholar 

  56. Yang J, Hu X, Wu M, Ma Y, Zhang X, Chen M, Yuan Y, Han R, Liu R, Guan S, Deng J, Xu S, Gao X, Xu S, Shuai Z, Jiang S, Guan S, Chen L, Pan F (2019) TNFAIP3 genetic polymorphisms reduce ankylosing spondylitis risk in Eastern Chinese Han population. Sci Rep 9:10209. https://doi.org/10.1038/s41598-019-46647-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chen WC, Wei JC, Lu HF, Wong HS, Woon PY, Hsu YW, Huang JD, Chang WC (2017) rs657075 (CSF2) Is associated with the disease phenotype (BAS-G) of ankylosing spondylitis. Int J Mol Sci 18:83. https://doi.org/10.3390/ijms18010083

    Article  CAS  PubMed Central  Google Scholar 

  58. Liu Y, Helms C, Liao W, Zaba LC, Duan S, Gardner J, Wise C, Miner A, Malloy MJ, Pullinger CR, Kane JP, Saccone S, Worthington J, Bruce I, Kwok PY, Menter A, Krueger J, Barton A, Saccone NL, Bowcock AM (2008) A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet 4:e1000041. https://doi.org/10.1371/journal.pgen.1000041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Coit P, Kaushik P, Caplan L, Kerr GS, Walsh JA, Dubreuil M, Reimold A, Sawalha AH (2019) Genome-wide DNA methylation analysis in ankylosing spondylitis identifies HLA-B*27 dependent and independent DNA methylation changes in whole blood. J Autoimmun 102:126–132. https://doi.org/10.1016/j.jaut.2019.04.022

    Article  CAS  PubMed  Google Scholar 

  60. Bowes J, Loehr S, Budu-Aggrey A, Uebe S, Bruce IN, Feletar M, Marzo-Ortega H, Helliwell P, Ryan AW, Kane D, Korendowych E, Alenius GM, Giardina E, Packham J, McManus R, FitzGerald O, Brown MA, Behrens F, Burkhardt H, McHugh N, Huffmeier U, Ho P, Reis A, Barton A (2015) PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further PsA-specific risk locus. Ann Rheum Dis 74:1882–1885. https://doi.org/10.1136/annrheumdis-2014-207187

    Article  CAS  PubMed  Google Scholar 

  61. Liu J, Pu W, Li Y, Ma Y, Zhu Q, Wan W, Yang C, Wang X, Chen X, Zhou X, Reveille JD, Jin L, Zou H, Wang J (2019) Genetic association of non-MHC region with ankylosing spondylitis in a Chinese population. Ann Rheum Dis 78:852–853. https://doi.org/10.1136/annrheumdis-2018-214625

    Article  PubMed  Google Scholar 

  62. Cotsapas C, Voight BF, Rossin E, Lage K, Neale BM, Wallace C, Abecasis GR, Barrett JC, Behrens T, Cho J, De Jager PL, Elder JT, Graham RR, Gregersen P, Klareskog L, Siminovitch KA, van Heel DA, Wijmenga C, Worthington J, Todd JA, Hafler DA, Rich SS, Daly MJ, FOCiS Network of Consortia (2011) Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet 7:e1002254. https://doi.org/10.1371/journal.pgen.1002254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Piñero J, Bravo À, Queralt-Rosinach N, Gutiérrez-Sacristán A, Deu-Pons J, Centeno E, García-García J, Sanz F, Furlong LI (2017) DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res 45:D833–D839. https://doi.org/10.1093/nar/gkw943

    Article  CAS  PubMed  Google Scholar 

  64. Brown KR, Otasek D, Ali M, McGuffin MJ, Xie W, Devani B, Toch IL, Jurisica I (2009) NAViGaTOR: Network Analysis, Visualization and Graphing Toronto. Bioinformatics 25:3327–3329. https://doi.org/10.1093/bioinformatics/btp595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. David T, Ling SF, Barton A (2018) Genetics of immune-mediated inflammatory diseases. Clin Exp Immunol 193:3–12. https://doi.org/10.1111/cei.13101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. McGonagle D, McDermott MF (2006) A proposed classification of the immunological diseases. PLoS Med 3:e297. https://doi.org/10.1371/journal.pmed.0030297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Quan C, Ren YQ, Xiang LH, Sun LD, Xu AE, Gao XH, Chen HD, Pu XM, Wu RN, Liang CZ, Li JB, Gao TW, Zhang JZ, Wang XL, Wang J, Yang RY, Liang L, Yu JB, Zuo XB, Zhang SQ, Zhang SM, Chen G, Zheng XD, Li P, Zhu J, Li YW, Wei XD, Hong WS, Ye Y, Zhang Y, Wu WS, Cheng H, Dong PL, Hu DY, Li Y, Li M, Zhang X, Tang HY, Tang XF, Xu SX, He SM, Lv YM, Shen M, Jiang HQ, Wang Y, Li K, Kang XJ, Liu YQ, Sun L, Liu ZF, Xie SQ, Zhu CY, Xu Q, Gao JP, Hu WL, Ni C, Pan TM, Li Y, Yao S, He CF, Liu YS, Yu ZY, Yin XY, Zhang FY, Yang S, Zhou Y, Zhang XJ (2010) Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC. Nat Genet 42:614–618. https://doi.org/10.1038/ng.603

    Article  CAS  PubMed  Google Scholar 

  68. Sawai H, Nishida N, Khor SS, Honda M, Sugiyama M, Baba N, Yamada K, Sawada N, Tsugane S, Koike K, Kondo Y, Yatsuhashi H, Nagaoka S, Taketomi A, Fukai M, Kurosaki M, Izumi N, Kang JH, Murata K, Hino K, Nishina S, Matsumoto A, Tanaka E, Sakamoto N, Ogawa K, Yamamoto K, Tamori A, Yokosuka O, Kanda T, Sakaida I, Itoh Y, Eguchi Y, Oeda S, Mochida S, Yuen MF, Seto WK, Poovorawan Y, Posuwan N, Mizokami M, Tokunaga K (2018) Genome-wide association study identified new susceptible genetic variants in HLA class I region for hepatitis B virus-related hepatocellular carcinoma. Sci Rep 8:7958. https://doi.org/10.1038/s41598-018-26217-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Rahmati S, Abovsky M, Pastrello C, Kotlyar M, Lu R, Cumbaa CA, Rahman P, Chandran V, Jurisica I (2020) pathDIP 4: an extended pathway annotations and enrichment analysis resource for human, model organisms and domesticated species. Nucleic Acids Res 48:D479–D488. https://doi.org/10.1093/nar/gkz989

    Article  CAS  PubMed  Google Scholar 

  70. Rahman P, Sun S, Peddle L, Snelgrove T, Melay W, Greenwood C, Gladman D (2006) Association between the interleukin-1 family gene cluster and psoriatic arthritis. Arthritis Rheum 54:2321–2325. https://doi.org/10.1002/art.21928

    Article  CAS  PubMed  Google Scholar 

  71. Reveille JD (2012) Genetics of spondyloarthritis--beyond the MHC. Nat Rev Rheumatol 8:296–304. https://doi.org/10.1038/nrrheum.2012.41

    Article  CAS  PubMed  Google Scholar 

  72. Gudjonsson JE, Thorarinsson AM, Sigurgeirsson B, Kristinsson KG, Valdimarssonn H (2003) Streptococcal throat infections and exacerbation of chronic plaque psoriasis: a prospective study. Br J Dermatol 149:530–534. https://doi.org/10.1046/j.1365-2133.2003.05552.x

  73. Gudjonsson JE, Karason A, Runarsdottir EH, Antonsdottir AA, Hauksson VB, Jónsson HH, Gulcher J, Stefansson K, Valdimarsson H (2006) 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 126:740–745. https://doi.org/10.1038/sj.jid.5700118

  74. Patel RV, Weinberg JM (2008) Psoriasis in the patient with human immunodeficiency virus, part 1: review of pathogenesis. Cutis 82:117–122

    PubMed  Google Scholar 

  75. Jin Y, Yang S, Zhang F, Kong Y, Xiao F, Hou Y, Fan X, Zhang X (2009) Combined effects of HLA-Cw6 and cigarette smoking in psoriasis vulgaris: a hospital-based case-control study in China. J Eur Acad Dermatol Venereol 23:132–137. https://doi.org/10.1111/j.1468-3083.2008.02951.x

  76. Setty AR, Curhan G, Choi HK (2007) Smoking and the risk of psoriasis in women: Nurses’ Health Study II. Am J Med 120:953–959. https://doi.org/10.1016/j.amjmed.2007.06.020

  77. Setty AR, Curhan G, Choi HK (2007) Obesity, waist circumference, weight change, and the risk of psoriasis in women: Nurses’ Health Study II. Arch Intern Med 167:1670–1675. https://doi.org/10.1136/ard.2007.073932

  78. Pattison E, Harrison BJ, Griffiths CE, Silman AJ, Bruce IN (2008) Environmental risk factors for the development of psoriatic arthritis: results from a case-control study. Ann Rheum Dis 67:672–676. https://doi.org/10.1136/ard.2007.073932

  79. Reveille JD, Williams FM (2006) Infection and musculoskeletal conditions: rheumatologic complications of HIV infection. Best Pract Res Clin Rheumatol 20:1159–1179. https://doi.org/10.1016/j.berh.2006.08.015

  80. Eder L, Law T, Chandran V, Shanmugarajah S, Shen H, Rosen CF, Cook RJ, Gladman DD (2011) Association between environmental factors and onset of psoriatic arthritis in patients with psoriasis. Arthritis Care Res 63:1091–1097. https://doi.org/10.1002/acr.20496

    Article  Google Scholar 

  81. Thorarensen SM, Lu N, Ogdie A, Gelfand JM, Choi HK, Love TJ (2017) Physical trauma recorded in primary care is associated with the onset of psoriatic arthritis among patients with psoriasis. Ann Rheum Dis 76:521–525. https://doi.org/10.1136/annrheumdis-2016-209334

    Article  PubMed  Google Scholar 

  82. Nguyen UDT, Zhang Y, Lu N, Louie-Gao Q, Niu J, Ogdie A, Gelfand JM, LaValley MP, Dubreuil M, Sparks JA, Karlson EW, Choi HK (2018) Smoking paradox in the development of psoriatic arthritis among patients with psoriasis: a population-based study. Ann Rheum Dis 77:119–123. https://doi.org/10.1136/annrheumdis-2017-211625

    Article  PubMed  Google Scholar 

  83. Duffin KC, Freeny IC, Schrodi SJ, Wong B, Feng BJ, Soltani-Arabshahi R, Rakkhit T, Goldgar DE, Krueger GG (2009) Association between IL13 polymorphisms and psoriatic arthritis is modified by smoking. J Invest Dermatol 129:2777–2783. https://doi.org/10.1038/jid.2009.169

    Article  CAS  PubMed  Google Scholar 

  84. Budu-Aggrey A, Brumpton B, Tyrrell J, Watkins S, Modalsli EH, Celis-Morales C, Ferguson LD, Vie GÅ, Palmer T, Fritsche LG, Løset M, Nielsen JB, Zhou W, Tsoi LC, Wood AR, Jones SE, Beaumont R, Saunes M, Romundstad PR, Siebert S, McInnes IB, Elder JT, Davey Smith G, Frayling TM, Åsvold BO, Brown SJ, Sattar N, Paternoster L (2019) Evidence of a causal relationship between body mass index and psoriasis: a mendelian randomization study. PLoS Med 16:e1002739. https://doi.org/10.1371/journal.pmed.1002739

    Article  PubMed  PubMed Central  Google Scholar 

  85. Thomsen RS, Nilsen TI, Haugeberg G, Gulati AM, Kavanaugh A, Hoff M (2019) Adiposity and physical activity as risk factors for developing psoriatic arthritis. Longitudinal data from the HUNT study. Arthritis Care Res. https://doi.org/10.1002/acr.24121

  86. Eder L, Abji F, Rosen CF, Chandran V, Gladman DD (2017) The association between obesity and clinical features of psoriatic arthritis: a case-control study. J Rheumatol 44:437–443. https://doi.org/10.3899/jrheum.160532

    Article  PubMed  Google Scholar 

  87. Haddad A, Johnson SR, Somaily M, Fazelzad R, Kron AT, Chau C, Chandran V (2015) Psoriatic arthritis mutilans: clinical and radiographic criteria. A systematic review. J Rheumatol 42:1432–1438. https://doi.org/10.3899/jrheum.141545

    Article  PubMed  Google Scholar 

  88. Patrick MT, Stuart PE, Raja K, Gudjonsson JE, Tejasvi T, Yang J, Chandran V, Das S, Callis-Duffin K, Ellinghaus E, Enerbäck C, Esko T, Franke A, Kang HM, Krueger GG, Lim HW, Rahman P, Rosen CF, Weidinger S, Weichenthal M, Wen X, Voorhees JJ, Abecasis GR, Gladman DD, Nair RP, Elder JT, Tsoi LC (2018) Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients. Nat Commun 9:4178. https://doi.org/10.1038/s41467-018-06672-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

Sara Rahmati is supported by a National Psoriasis Foundation Early Career grant and a grant from the Atlantic Innovation Fund, Canada. Proton Rahman is supported by a grant from the Atlantic Innovation Fund, Canada. Vinod Chandran is supported by a Pfizer Chair Research Award, Rheumatology, University of Toronto, Canada.

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Authors and Affiliations

  1. Schroeder Arthritis Institute, Krembil Research Institute, University Heath Network, Toronto, Ontario, Canada

    Sara Rahmati & Vinod Chandran

  2. Department of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada

    Sara Rahmati, Quan Li, Proton Rahman & Vinod Chandran

  3. Division of Rheumatology Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    Vinod Chandran

  4. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Vinod Chandran

  5. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

    Vinod Chandran

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  1. Sara Rahmati
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Correspondence to Vinod Chandran.

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This article is a contribution to the special issue on: Spondyloarthritis - Guest Editors: Robert Inman & Nigil Haroon

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Supplementary information

ESM 1

List of variant genest/choromosomal locations shared between AS and PsA (Set A), AS but not to PsA (Set B), PsA but not to AS (Set C) (xlsx 372 kb)

ESM 2

Enriched pathways in variant genes in Set A(PsA but not AS) (xlsx 372 kb)

ESM 3

Enriched pathways in variant genes in Set B (AS but not PsA) (xlsx 372 kb)

ESM 4

Enriched pathways in variant genes in Set C (shared between AS and PsA) (xlsx 372 kb)

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Rahmati, S., Li, Q., Rahman, P. et al. Insights into the pathogenesis of psoriatic arthritis from genetic studies. Semin Immunopathol 43, 221–234 (2021). https://doi.org/10.1007/s00281-021-00843-2

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