{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:16:20Z","timestamp":1791994580644,"version":"4.4.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2508100"],"award-info":[{"award-number":["2023YFC2508100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The association between psoriasis vulgaris and bullous pemphigoid (BP) remains largely unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate whether there is a causal effect between psoriasis vulgaris and BP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two-sample bidirectional Mendelian randomization (MR) analyses were conducted using publicly released genome-wide association studies (GWAS) summary statistics. The GWAS summary statistics for BP were downloaded online from FinnGen Biobank Documentation of the R12 release, which includes 219 BP cases and 218,066 controls. The GWAS data for psoriasis vulgaris were extracted from Sakaue et\u00a0al., which comprises 5072 cases and 478,102 controls. Single-nucleotide polymorphisms (SNPs) associated with exposure were selected as instrumental variables by performing additional quality control steps. The inverse-variance-weighted (IVW) method was used for the primary MR analyses, and the MR-Egger regression, weighted mode method, weighted median method, and simple mode were employed for sensitivity analyses. The MR-Egger intercept test and \u201cleave-one-out\u201d sensitivity analysis were performed to evaluate the horizontal pleiotropy and the potentially influential SNPs, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetically determined log odds of psoriasis vulgaris were associated with an increased risk of BP (IVW: odds ratio (OR) = 1.263, 95% confidence interval (CI): 1.013-1.575, <jats:italic>P<\/jats:italic>=0.038). Sensitivity analyses by the weighted mode (OR=1.255, 95%CI: 0.973-1.618, <jats:italic>P<\/jats:italic>=0.106), MR Egger (OR=1.315, 95%CI: 0.951-1.817, <jats:italic>P<\/jats:italic>=0.126), simple mode (OR=1.414, 95%CI: 0.823-2.429, <jats:italic>P<\/jats:italic>=0.234) and weighted median method (OR=1.177, 95%CI: 0.889-1.559, <jats:italic>P<\/jats:italic>=0.254) derived directionally consistent relationship between the genetically predicted log odds of psoriasis vulgaris and risks of developing BP. On the contrary, we found that genetically predicted BP had no significant effect on psoriasis vulgaris (IVW: OR=0.996, <jats:italic>P<\/jats:italic>= 0.707), indicating the unidirectionality of the relationship. MR-Egger intercept tests showed no evidence of horizontal pleiotropy. No influential SNP driving the results was detected by the leave-one-out sensitivity analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results suggested that psoriasis vulgaris causally increases the risk of BP, highlighting the need for potential strategies for the prevention and early diagnosis of comorbid BP in patients with psoriasis vulgaris. Further researches into this association and underlying mechanisms are warranted.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1365118","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T04:47:05Z","timestamp":1710305225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Causal association between psoriasis vulgaris and bullous pemphigoid: a two-sample bidirectional Mendelian randomization study"],"prefix":"10.3389","volume":"15","author":[{"given":"Aobei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m1590","article-title":"National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study","volume":"369","author":"Parisi","year":"2020","journal-title":"BMJ (Clinical Res ed.)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32549-6","article-title":"Psoriasis","volume":"397","author":"Griffiths","year":"2021","journal-title":"Lancet (London England)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2016.09.004","article-title":"Psoriasis and autoimmunity","volume":"15","author":"Sticherling","year":"2016","journal-title":"Autoimmun Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.05.023","article-title":"Melanocytes: target cells of an HLA-C*06:02-restricted autoimmune response in psoriasis","volume":"137","author":"Prinz","year":"2017","journal-title":"J Invest Dermatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12891","article-title":"Autoimmunity and autoimmune co-morbidities in psoriasis","volume":"154","author":"Furue","year":"2018","journal-title":"Immunology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00954","article-title":"Human leukocyte antigen-class I alleles and the autoreactive T cell response in psoriasis pathogenesis","volume":"9","author":"Prinz","year":"2018","journal-title":"Front In Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2006.02861.x","article-title":"Concomitant psoriasis and bullous pemphigoid: coincidence or pathogenic relationship","volume":"45","author":"Wilczek","year":"2006","journal-title":"Int J Dermatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2017.02.057","article-title":"Association between bullous pemphigoid and psoriasis: A case-control study","volume":"77","author":"Kridin","year":"2017","journal-title":"J Am Acad Dermatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2018.06.026","article-title":"Increased risks of autoimmune rheumatic diseases in patients with psoriasis: A nationwide population-based study","volume":"79","author":"Ju","year":"2018","journal-title":"J Am Acad Dermatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2017.03.010","article-title":"Bullous pemphigoid","volume":"16","author":"Ba\u011fc\u0131","year":"2017","journal-title":"Autoimmun Rev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61140-4","article-title":"Pemphigoid diseases","volume":"381","author":"Schmidt","year":"2013","journal-title":"Lancet (London England)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012615-044313","article-title":"Mechanisms of disease: pemphigus and bullous pemphigoid","volume":"11","author":"Hammers","year":"2016","journal-title":"Annu Rev Pathol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/biom10101432","article-title":"Bullous pemphigoid: trigger and predisposing factors","volume":"10","author":"Moro","year":"2020","journal-title":"Biomolecules"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2015.03.016","article-title":"Coexistence of autoimmune bullous diseases (AIBDs) and psoriasis: A series of 145 cases","volume":"73","author":"Ohata","year":"2015","journal-title":"J Am Acad Dermatol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.14902","article-title":"Psoriasis is associated with increased risk of bullous pemphigoid: A nationwide population-based cohort study in Taiwan","volume":"46","author":"Ho","year":"2019","journal-title":"J Dermatol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.12899","article-title":"Association between bullous pemphigoid and psoriasis: Systematic review and meta-analysis of case-control studies","volume":"60","author":"Phan","year":"2019","journal-title":"Australas J Dermatol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328","article-title":") Mendelian randomization: genetic anchors for causal inference in epidemiological studies","volume":"23","author":"Davey Smith","year":"2014","journal-title":"Hum Mol Genet"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601","article-title":"Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians","volume":"362","author":"Davies","year":"2018","journal-title":"BMJ (Clinical Res ed.)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.17219","article-title":"Mendelian randomization","volume":"318","author":"Emdin","year":"2017","journal-title":"JAMA"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00931-x","article-title":"A cross-population atlas of genetic associations for 220 human phenotypes","volume":"53","author":"Sakaue","year":"2021","journal-title":"Nat Genet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14869","article-title":"Assessment of relationships between bullous pemphigoid and neurological diseases: A bidirectional two-sample Mendelian randomization study","volume":"33","author":"Shen","year":"2023","journal-title":"Exp Dermatol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwt084","article-title":"Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators","volume":"178","author":"Pierce","year":"2013","journal-title":"Am J Epidemiol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16127","article-title":"High plasma 25-hydroxyvitamin D and high risk of nonmelanoma skin cancer: a Mendelian randomization study of 97 849 individuals","volume":"178","author":"Winsl\u00f8w","year":"2018","journal-title":"Br J Dermatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.11.025","article-title":"Causal relationship and shared genetic loci between psoriasis and type 2 diabetes through trans-disease meta-analysis","volume":"141","author":"Patrick","year":"2021","journal-title":"J Invest Dermatol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2022.06.015","article-title":"Serum lipids and risk of incident psoriasis: A prospective cohort study from the UK biobank study and mendelian randomization analysis","volume":"142","author":"Xiao","year":"2022","journal-title":"J Invest Dermatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2022.04.021","article-title":"Genome-wide integration of genetic and genomic studies of atopic dermatitis: insights into genetic architecture and pathogenesis","volume":"142","author":"Chen","year":"2022","journal-title":"J Invest Dermatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.2011.165.issue-3","article-title":"Comorbidity profiles among patients with bullous pemphigoid: a nationwide population-based study","volume":"165","author":"Chen","year":"2011","journal-title":"Br J Dermatol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-022-02372-w","article-title":"Association between bullous pemphigoid and atopic dermatitis: a population-based case-control study in Taiwan","volume":"315","author":"Wu","year":"2023","journal-title":"Arch Dermatol Res"},{"key":"B29","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1093\/ije\/dyh132","article-title":"Mendelian randomization: prospects, potentials, and limitations","volume":"33","author":"Smith","year":"2004","journal-title":"Int J Epidemiol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/jde.2011.38.issue-12","article-title":"Analysis of psoriasis patients registered with the Japanese Society for Psoriasis Research from 2002-2008","volume":"38","author":"Takahashi","year":"2011","journal-title":"J Dermatol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21300","article-title":"Transcriptional responses of human epidermal keratinocytes to cytokine interleukin-1","volume":"214","author":"Yano","year":"2008","journal-title":"J Cell Physiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14791","article-title":"Interleukin-36 cytokines are overexpressed in the skin and sera of patients with bullous pemphigoid","volume":"32","author":"Maglie","year":"2023","journal-title":"Exp Dermatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.1998.02169.x","article-title":"Cytokine pattern in blister fluid and serum of patients with bullous pemphigoid: relationships with disease intensity","volume":"138","author":"Ameglio","year":"1998","journal-title":"Br J Dermatol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12400","article-title":"Psoriasis and basement-membrane laminin","volume":"169","author":"McFadden","year":"2013","journal-title":"Br J Dermatol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1159\/000330330","article-title":"Th1, Th2, Th17 and regulatory T cell pattern in psoriatic patients: modulation of cytokines and gene targets induced by etanercept treatment and correlation with clinical response","volume":"223","author":"Quaglino","year":"2011","journal-title":"Dermatol (Basel Switzerland)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-018-8668-1","article-title":"Psoriasis: from pathogenesis to targeted therapies","volume":"54","author":"Conrad","year":"2018","journal-title":"Clin Rev In Allergy Immunol"},{"key":"B37","article-title":"Cytokines and bullous pemphigoid","volume":"10","author":"D'Auria","year":"1999","journal-title":"Eur Cytokine Network"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01383","article-title":"Role of the pruritic cytokine IL-31 in autoimmune skin diseases","volume":"10","author":"Gibbs","year":"2019","journal-title":"Front In Immunol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1080\/07853890.2020.1742367","article-title":"Factors associated with the activity and severity of bullous pemphigoid: a review","volume":"52","author":"Liu","year":"2020","journal-title":"Ann Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14209","article-title":"Distinct compartmentalization of immune cells and mediators characterizes bullous pemphigoid disease","volume":"29","author":"Margaroli","year":"2020","journal-title":"Exp Dermatol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"328","DOI":"10.3390\/jcm12010328","article-title":"The intriguing links between psoriasis and bullous pemphigoid","volume":"12","author":"Maronese","year":"2022","journal-title":"J Clin Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-022-00719-7","article-title":"Management of coexisting bullous pemphigoid and psoriasis: A review","volume":"23","author":"Hsieh","year":"2022","journal-title":"Am J Clin Dermatol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.2011.04102.x","article-title":"Drug-induced bullous pemphigoid: cases triggered by intravenous iodine and etanercept","volume":"36","author":"Kluk","year":"2011","journal-title":"Clin Exp Dermatol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.13909","article-title":"Development of bullous pemphigoid during secukinumab treatment for psoriasis","volume":"44","author":"Ho","year":"2017","journal-title":"J Dermatol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1136\/ejhpharm-2018-001849","article-title":"Bullous pemphigoid induced by ustekinumab: a case report","volume":"28","author":"Marin","year":"2021","journal-title":"Eur J Hosp Pharm Sci Pract"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0781.1995.tb00166.x","article-title":"Bullous pemphigoid possibly induced by psoralen plus ultraviolet A therapy","volume":"11","author":"George","year":"1995","journal-title":"Photodermatol Photoimmunol Photomedicine"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2021.05.013","article-title":"Development of psoriasis during treatment with dupilumab: A systematic review","volume":"86","author":"Brumfiel","year":"2022","journal-title":"J Am Acad Dermatol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/dth.15754","article-title":"Concurrent bullous pemphigoid and plaque psoriasis successfully treated with Janus kinase inhibitor Baricitinib","volume":"35","author":"Xiao","year":"2022","journal-title":"Dermatologic Ther"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110591","article-title":"Concurrent bullous pemphigoid and psoriasis vulgaris successfully treated with Janus kinase inhibitor tofacitinib: A case report and review of the literature","volume":"122","author":"Li","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1186\/s12916-020-01778-5","article-title":"Mendelian randomization study of inflammatory bowel disease and bone mineral density","volume":"18","author":"Wu","year":"2020","journal-title":"BMC Med"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.2217\/epi.15.88","article-title":"Mendelian randomization: applications and limitations in epigenetic studies","volume":"7","author":"Relton","year":"2015","journal-title":"Epigenomics"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.114.104497","article-title":"Genetically high plasma vitamin C, intake of fruit and vegetables, and risk of ischemic heart disease and all-cause mortality: a Mendelian randomization study","volume":"101","author":"Kobylecki","year":"2015","journal-title":"Am J Clin Nutr"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2023.1151837","article-title":"Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis","volume":"11","author":"Dai","year":"2023","journal-title":"Front In Public Health"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1365118\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T04:47:08Z","timestamp":1710305228000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1365118\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,13]]},"references-count":53,"alternative-id":["10.3389\/fimmu.2024.1365118"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1365118","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,13]]},"article-number":"1365118"}}