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Exploring genetic targets of psoriasis using genome wide association studies (GWAS) for drug repurposing

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Abstract

Psoriasis is a chronic inflammatory disease causing itching in the body and pain in the joints. Currently, no permanent cure is available at a commercial level for this disease. Genome wide association studies (GWAS) provide a deeper insight that helps in better understanding this disease and further possible cure of this disease. The major goal of the present study is to identify potent genetic targets of psoriasis disease using GWAS approach and identify drugs for repurposing. The methods used include GWAS catalogue, GeneAnalytics, canSAR protein annotation tool, VarElect, Drug bank, Proteomics database, ProTox software. By exploring GWAS catalogue, 126 psoriasis associated genes (PAG) were identified. 68 genes found to be druggable were obtained from canSAR protein annotation tool. Localization results depict that maximum genes are present in cytoplasmic cellular components. The superpathways obtained from GeneAnalytics resulted in involvement of these genes in the immune system, Jak/Stat pathway, Th17 and Wnt pathways. Two genes Interleukin 13 (IL13) and POLI are Food and Drug Administration (FDA) approved targets. Small compounds for these targets were analysed for drug-likeliness, toxicity and mutagenecity properties. The FDA approved drug pandel was found to possess desirable properties. The medications used for psoriasis causes mild to severe side effects and does not work well always. Hence we propose drug repurposing strategy to use existing drugs for new therapies. Therefore, the drug pandel could be explored further and repurposed to treat psoriasis.

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References

  • Ayala-Fontánez N, Soler DC, McCormick TS (2016) Current knowledge on psoriasis and autoimmune diseases. Psoriasis (Auckl) 6:7–32

    Google Scholar 

  • Bandoli G, Johnson DL, Jones KL, Lopez Jiminez J, Salas E, Mirrasoul N et al (2010) Potentially modifiable risk factors for adverse pregnancy outcomes in women with psoriasis. Br J Dermatol 163:334–339

    CAS  PubMed  Google Scholar 

  • Bieler S (2019) New psoriasis treatment guidelines announced. The first two AAD-NPF guidelines in a series of six tackle biologics and comorbidities. https://www.psoriasis.org/advance/new-psoriasis-treatment-guidelines-announced

  • Bulusu KC, Tym JE, Coker EA, Schierz AC, Al-Lazikani B (2014) canSAR: updated cancer research and drug discovery knowledgebase. Nucl Acids Res 42(Database issue):D1040–D1047

    PubMed  PubMed Central  Google Scholar 

  • Calabrese GM, Mesner LD, Stains JP, Tommasini SM, Horowitz MC, Rosen CJ, Farber CR (2016) Integrating GWAS and co-expression network data identifies bone mineral density genes SPTBN1 and MARK3 and an osteoblast functional module. Cell Syst 4(1):1–14

    Google Scholar 

  • Chimenti MS, Ballanti E, Perricone C, Cipriani P, Giacomelli R, Perricone R (2013a) Immunomodulation in psoriatic arthritis: focus on cellular and molecular pathways. AutoimmunRev 12(5):599–606

    CAS  Google Scholar 

  • Chimenti MS, Ballanti E, Perricone C, Cipriani P, Giacomelli R, Perricone R (2013b) Immunomodulation in psoriatic arthritis: focus on cellular and molecular pathways. Autoimmun Rev 12(5):599–606

    CAS  PubMed  Google Scholar 

  • Dehkharghani RA, Hosseinzadeh M, Nezafatdoost F et al (2018) Application of methodological analysis for hydrocortisone nanocapsulation in biodegradable polyester and MTT assay. Polym Sci Ser A 60:770

    CAS  Google Scholar 

  • Denny JC, Bastarache L, Ritchie MD, Carroll RJ, Zink R et al (2013) Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data. Nat Biotechnol 31(12):1102–1111

    CAS  PubMed  PubMed Central  Google Scholar 

  • Drwal MN, Banerjee P, Dunkel M, Wettig MR, Preissner R (2014) ProTox: a web server for the in silico prediction of rodent oral toxicity. Nucl Acids Res 42(W1):53–58

    Google Scholar 

  • Fitzgerald O, Winchester R (2009) Psoriatic arthritis: from pathogenesis to therapy. Arthritis Res Ther 11(1):214

    PubMed  PubMed Central  Google Scholar 

  • Fitzgerald O, Haroon M, Giles JT, Winchester R (2015) Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype. Arthritis Res Ther 17(1):115

    PubMed  PubMed Central  Google Scholar 

  • Gelfand JM, Gladman DD, Mease PJ, Smith N, Margolis DJ, Nijsten T et al (2005) Epidemiology of psoriatic arthritis in the population of the United States. J Am Acad Dermatol 53(4):573

    PubMed  Google Scholar 

  • Gladman DD, Antoni C, Mease P, Clegg DO, Nash P (2005) Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis 64:14–17

    Google Scholar 

  • Gottesman O, Kuivaniemi H, Tromp G, Faucett WA, Li R et al (2013) The electronic medical records and genomics (eMERGE) network: past, present, and future. Genet med 15(10):761–771

    PubMed  PubMed Central  Google Scholar 

  • Gupta MA, Gupta AK (2003) Psychiatric and psychological comorbidity in patients with dermatologic disorders: epidemiology and management. Am J Clin Dermatol 4:833e42

  • Halling-Brown MD, Bulusu KC, Patel M, Tym JE, Al-Lazikani B (2012) canSAR: an integrated cancer public translational research and drug discovery resource. Nucl acids Res 40(Database issue):D947–D956

    PubMed  PubMed Central  Google Scholar 

  • Harel A et al (2009) GIFtS: annotation landscape analysis with GeneCards. BMC Bioinform 10:348

    Google Scholar 

  • Haroon M, FitzGerald O, Winchester R (2013) Epidemiology, genetics and management of psoriatic arthritis: focus on developments of who develops the disease, its clinical features, and emerging treatment options. Psoriasis Targets Ther 3:11–23

    Google Scholar 

  • Helliwell P, Wright V (1997) Psoriatic arthritis: clinical features. Rheumatology 21:1–8

    Google Scholar 

  • Kim MS, Pinto SM, Getnet D, Nirujogi RS, Manda SS et al (2014) A draft map of the human proteome. Nature 509(7502):575–581

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kolker E, Higdon R, Haynes W, Welch D, Broomall W et al (2012) MOPED: model organism protein expression database. Nucl Acids Res 40(Database issue):D1093–D1099

    PubMed  PubMed Central  Google Scholar 

  • Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM (2010) The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol 146:891e5

  • Law V, Knox C, Djoumbou Y, Jewison T, Guo AC et al (2014) DrugBank 4.0: shedding new light on drug metabolism. Nucl Acids Res 42(Database issue): D1091–D1097

    PubMed  PubMed Central  Google Scholar 

  • Lipinski CA (2004) Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 4:337–341

    Google Scholar 

  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46(1–3):3–26

    CAS  PubMed  Google Scholar 

  • Lofvendahl S, Theander E, Svensson A, Carlsson KS, Englund M, Petersson IF (2014) Validity of diagnostic codes and prevalence of physician-diagnosed psoriasis and psoriatic arthritis in southern Sweden—a population-based register study. PLoS ONE 9(5):e98024

    PubMed  PubMed Central  Google Scholar 

  • McGeachie MJ, Clemmer GL, Lasky-Su J, Dahlin A, Raby BA, Weiss ST (2014) Joint GWAS analysis: comparing similar GWAS at different genomic resolutions identifies novel pathway associations with six complex diseases. Genom Data 1(2):202–211

    Google Scholar 

  • Narayanan R (2015) Druggable vitiligo genome: a fast track approach to take the genome wide association to the clinic. MOJ Proteom Bioinform 2(3):102–110

    Google Scholar 

  • Nast A, Erdmann R, Pathirana D et al (2008) Translating psoriasis treatment guidelines into clinical practice – the need for educational interventions and strategies for broad dissemination. J Eval Clin Pract 14:803–806

    PubMed  Google Scholar 

  • Oprea TI, Davis AM, Teague SJ, Leeson PD (2001) Is there a difference between leads and drugs A historical perspective. J Chem Inf Comput Sci 41(5):1308–1315

    CAS  PubMed  Google Scholar 

  • Porter ML, Lockwood SJ, Kimball AB (2017) Update on biologic safety for patients with psoriasis during pregnancy. Int J Women Dermatol 3:21–25

    Google Scholar 

  • Postmus I, Trompet S, Deshmukh HA, Barnes MR, Li X, Warren HR et al (2014) Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. Nat commun 5:5068

    CAS  PubMed  Google Scholar 

  • Rapp SR, Exum ML, Reboussin DM, Feldman SR, Fleischer A, Clark A (1997) The physical, psychological and social impact of psoriasis. J Health Psychol 2:525e37

    CAS  PubMed  Google Scholar 

  • Richards HL, Fortune DG, Griffiths CE, Main CJ (2001) The contribution of perceptions of stigmatisation to disability in patients with psoriasis. J Psychosom Res 50:11e5

    CAS  PubMed  Google Scholar 

  • Sabat R, Philipp S, Höflich C, Kreutzer S, Wallace E, Asadullah K et al (2007) Immunopathogenesis of psoriasis. Exp Dermatol 16(10):779–798

    CAS  PubMed  Google Scholar 

  • Safran M, Dalah I, Alexander J, Rosen N, Stein TI, Shmoish M, Nativ N, Bahir I, Doniger T, Krug H, Sirota-Madi A, Olender T, Golan Y, Stelzer G, Harel A, Lancet D (2010) GeneCards version 3: the human gene integrator. Database (Oxford) 2010:baq020

    Google Scholar 

  • Shungin D, Winkler TW, Croteau-Chonka DC, Ferreira T et al (2015) New genetic loci link adipose and insulin biology to body fat distribution. Nature 518(7538):187–196

    CAS  PubMed  PubMed Central  Google Scholar 

  • Simon-Sanchez J, Singleton A (2008) Genome-wide association studies in neurological disorders. Lancet Neurol 7(11):1067–1072

    CAS  PubMed  PubMed Central  Google Scholar 

  • Solovieff N, Cotsapas C, Lee PH, Purcell SM, Smoller JW (2013) Pleiotropy in complex traits: challenges and strategies. Nat Rev Genet 14:483–495

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stelzer G et al (2016) VarElect: the phenotype-based variation prioritizer of the GeneCards Suite”. BMC Genom 17(2):444

    Google Scholar 

  • Strand V, Sharp V, Koenig AS, Park G, Shi Y, Wang B et al (2012) Comparison of health-related quality of life in rheumatoid arthritis, psoriatic arthritis and psoriasis and effects of etanercept treatment. Ann Rheum Dis 71(7):1143–1150

    CAS  PubMed  Google Scholar 

  • Sundarrajan S, Arumugam M (2016) Comorbidities of psoriasis—exploring the links by network approach. PLoS One 11(3):e0149175 (3.05)

    PubMed  PubMed Central  Google Scholar 

  • Sundarrajan S, Lulu S, Arumugam M (2015) Insights into protein interaction networks reveal non-receptor kinases as significant druggable targets for psoriasis. Gene 566:138–147

    CAS  PubMed  Google Scholar 

  • Takeshita J et al (2017) Psoriasis and comorbid diseases. J Am Acad Dermatol 76:393–403

    PubMed  PubMed Central  Google Scholar 

  • The Gene Ontology Consortium (2008) The Gene Ontology project in 2008. Nucl Acids Res 36(Database issue):D440–D444

  • Torre K, Shahriari M (2017) Clinical trials in dermatology. Int J Women Dermatol 3:10–13

    Google Scholar 

  • Tu HP, Yu CL, Lan CCE, Yu S (2016) Prevalence of schizophrenia in patients with psoriasis: a nationwide study. Dermatol Sin 35(1):1–6

    Google Scholar 

  • Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P et al (2015) Proteomics. Tissue-based map of the human proteome. Science 347(6220):1260419

    PubMed  Google Scholar 

  • van Mierlo GJ, Cnubben NH, Wouters D, Wolbink GJ, Hart MH, Rispens T et al (2014) The minipig as an alternative non-rodent model for immunogenicity testing using the TNFalpha blockers adalimumab and infliximab. J Immunotoxicol 11(1):62–71

    PubMed  Google Scholar 

  • Velappan R, Venu S, Ramasamy S, Chellappan L (2019) Current scenario in clinical trends of psoriasis in tertiary care hospital. Int J Res Dermatol 5:452–456

    Google Scholar 

  • Welter D, MacArthur J, Morales J, Burdett T, Hall P et al (2014) The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucl Acids Res 42(Database issue):D1001–D1006

    PubMed  PubMed Central  Google Scholar 

  • Wilhelm M, Schlegl J, Hahne H, Moghaddas Gholami A et al (2014) Mass-spectrometry-based draft of the human proteome. Nature 509(7502):582–587

    CAS  PubMed  Google Scholar 

  • Wolk K, Haugen HS, Xu W, Witte E, Waggie K, Anderson M et al (2009) IL-22and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not. J Mol Med (Berl) 87(5):523–536

    CAS  Google Scholar 

  • Wolpin BM, Rizzato C, Kraft P, Kooperberg C, Petersen GM et al (2014) Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nat Genet 46(9):994–1000

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang HJ, Yang KC (2015) Impact of psoriasis on quality of life in Taiwan. Dermatol Sin 33:146e50

    Google Scholar 

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Acknowledgements

We would like to take this opportunity to thank VIT University for providing computational facility.

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AM: Conceived and designed the analysis. HN, NP: Collected data and implemented the analysis. RO: Helped in manuscript writing. JJ: Contributed data or analysis tools.

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Correspondence to Arumugam Mohanapriya.

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Nanda, H., Ponnusamy, N., Odumpatta, R. et al. Exploring genetic targets of psoriasis using genome wide association studies (GWAS) for drug repurposing. 3 Biotech 10, 43 (2020). https://doi.org/10.1007/s13205-019-2038-4

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