{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:10:50Z","timestamp":1790806250733,"version":"4.1.0"},"reference-count":90,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>In this work, we present a comprehensive overview of the genetic and non-genetic complexity of eosinophilic granulomatosis with polyangiitis (EGPA). EGPA is a rare complex systemic disease that occurs in people presenting with severe asthma and high eosinophilia. After briefly introducing EGPA and its relationship with the anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAVs), we delve into the complexity of this disease. At first, the two main biological actors, ANCA and eosinophils, are presented. Biological and clinical phenotypes related to ANCA positivity or negativity are explained, as well as the role of eosinophils and their pathological subtypes, pointing out their intricate relations with EGPA. Then, the genetics of EGPA are described, providing an overview of the research effort to unravel them. Candidate gene studies have investigated biologically relevant candidate genes; the more recent genome-wide association studies and meta-analyses, able to analyze the whole genome, have confirmed previous associations and discovered novel risk loci; in the end, family-based studies have dissected the contribution of rare variants and the heritability of EGPA. Then, we briefly present the environmental contribution to EGPA, reporting seasonal events and pollutants as triggering factors. In the end, the latest omic research is discussed and the most recent epigenomic, transcriptomic and microbiome studies are presented, highlighting the current challenges, open questions and suggesting approaches to unraveling this complex disease.<\/jats:p>","DOI":"10.3390\/cimb46070446","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T16:55:36Z","timestamp":1721321736000},"page":"7516-7529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genetic and Non-Genetic Contributions to Eosinophilic Granulomatosis with Polyangiitis: Current Knowledge and Future Perspectives"],"prefix":"10.3390","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9175-9455","authenticated-orcid":false,"given":"Mirko","family":"Treccani","sequence":"first","affiliation":[{"name":"GM Lab, Department of Surgery, Dentistry, Gynaecology and Paediatrics, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0413-6031","authenticated-orcid":false,"given":"Laura","family":"Veschetti","sequence":"additional","affiliation":[{"name":"Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milano, Italy"},{"name":"Vita-Salute San Raffaele University, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8678-9337","authenticated-orcid":false,"given":"Cristina","family":"Patuzzo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8705-8560","authenticated-orcid":false,"given":"Giovanni","family":"Malerba","sequence":"additional","affiliation":[{"name":"GM Lab, Department of Surgery, Dentistry, Gynaecology and Paediatrics, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Vaglio","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, Meyer Children\u2019s Hospital IRCCS, 50139 Florence, Italy"},{"name":"Department of Biomedical Experimental and Clinical Sciences \u201cMario Serio\u201d, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7572-7031","authenticated-orcid":false,"given":"Davide","family":"Martorana","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Onco-Hematology, University Hospital of Parma, 43126 Parma, Italy"},{"name":"CoreLab Unit, Research Center, University Hospital of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"ref_1","first-page":"277","article-title":"Allergic Granulomatosis, Allergic Angiitis, and Periarteritis Nodosa","volume":"27","author":"Churg","year":"1951","journal-title":"Am. 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